Advertisement

Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma

  • John C. Reed
  • Toshiyuki Miyashita
  • Stanislaw Krajewski
  • Shinichi Takayama
  • Christine Aime-Sempe
  • Shinichi Kitada
  • Takaaki Sato
  • Hong-Gang Wang
  • Masayoshi Harigai
  • Motoi Hanada
  • Maryla Krajewska
  • Kristine Kochel
  • Juan Millan
  • Hiroko Kobayashi
Part of the Cancer Treatment and Research book series (CTAR, volume 84)

Abstract

Members of the bcl-2 gene family play a central role in regulating the relative sensitivity and resistance of cells to a wide variety of apoptotic stimuli. The first member of this multigene family ,bcl-2, was discovered by virtue of its involvement in the t(14;18) chromosomal translocations commonly found in non-Hodgkin’s lymphomas [1–4]. Deregulation of the bcl-2 gene either by translocations in B-cell lymphomas or through other mechanisms in several other types of cancer, including acute and chronic leukemias, contributes to neoplastic cell expansion by prolonging cell survival rather than by accelerating rates of cell division [5–8]. The Bcl-2 protein also can protect tumor cells from apoptosis induced by radiation and nearly all cytotoxic anticancer drugs [9–12], thus potentially contributing to treatment failures in patients with cancer [13–16]. Several additional homologues of bcl-2 have recently been discovered in humans and other mammals, revealing the presence of a multigene family [17–20]. Moreover, homologues of bcl-2 have been discovered in some DNA viruses, including Epstein-Barr virus (EBV), which plays a significant role in the pathogenesis of some types of non-Hodgkin’s lymphomas and Hodgkin’s disease [21]. Interestingly, some members of the bcl-2 gene family function as inhibitors of cell death, similar to bcl-2, whereas others are promoters of apoptosis that oppose the actions of the Bcl-2 protein.

Keywords

Follicular Lymphoma Germinal Center African Swine Fever Virus Gene Transfer Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Tsujimoto Y, Cossman J, Jaffe E, Croce C (1985). Involvement of the bcl-2 gene in human follicular lymphoma. Science 288:1140–1443.Google Scholar
  2. 2.
    Tsujimoto Y, Cossman JA-J, Croce C (1985). Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440–1443.PubMedGoogle Scholar
  3. 3.
    Cleary ML, Smith SD, Sklar J (1986). Clonging and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47:19–28.PubMedGoogle Scholar
  4. 4.
    Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ (1985). Clonging the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 41:899–906.PubMedGoogle Scholar
  5. 5.
    Vaux DL, Cory S, Adams JM (1988). Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335:440–442.PubMedGoogle Scholar
  6. 6.
    Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990). Bcl-2 is an inner mitochondral membrane protein that blocks programmed cell death. Nature 348:334–336.PubMedGoogle Scholar
  7. 7.
    McDonnell TJ, Deane N, Platt FM, Numez G, Jaeger V, Mckearn JP, Korsmeyer SJ (1989). Bcl-2-immunoglobulin transgenic mice demonstrate extended B-cell survival and follicular lymphoproliferation. Cell 57:79–88.PubMedGoogle Scholar
  8. 8.
    Katsumata M, Siegel R, Louie D, Miyashita T, Tanaka S, Greene M, Reed JC (1992). Differential effects of bcl-2 on B- and T- lymphocytes in transgenic mice. Proc Natl Acad Sci USA 89:11376–11380.PubMedGoogle Scholar
  9. 9.
    Miyashita T, Reed JC (1992). BCL-2 gene transfer increases relative resistance of S49.1 and WEH17.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs. Cancer Res 52:5407–5411.PubMedGoogle Scholar
  10. 10.
    Miyashita T, Reed JC (1993). Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151–157.PubMedGoogle Scholar
  11. 11.
    Collins MKL, Marvel J, Malde P, Lopez-Rivas A (1992). Interleukin-3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents. J Exp Med 176:1043–1051.PubMedGoogle Scholar
  12. 12.
    Griffiths SD, Goodhead DT, Marsden SJ, Wright EG, Krajewski S, Reed JC, Korsmeyer SJ, Greaves M (1994). Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis. J Exp Med 179:1789–1797.PubMedGoogle Scholar
  13. 13.
    Yunis JJ, Mayer MG, Arensen MA, Aeppli DP, Oken MM, Frizzera G (1991). Bcl-2 and other genomic alterations in the prognosis of large-cell lymphomas. N Engl J Med 320:1047–1054.Google Scholar
  14. 14.
    Offit K, Koduru PRK, Hollis R, Filippa D, Jhanwar SC, Clarkson BC, Chaganti RSK (1989). 18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significance. Br J Haematol 72:178–183.PubMedGoogle Scholar
  15. 15.
    McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LWK, Hsieh J-T, Tu S-M, Campbell ML (1992). Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 52:6940–6944.PubMedGoogle Scholar
  16. 16.
    Campos L, Roualult, JP, Sabido O, Roubi N, Vasselon C, Archimbaud E, Magaud J-P, Guyotat D (1993). High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood 81:3091–3096.PubMedGoogle Scholar
  17. 17.
    Oltvai Z, Milliman C, Korsmeyer SJ (1993). Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619.PubMedGoogle Scholar
  18. 18.
    Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB (1993). bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74:597–608.PubMedGoogle Scholar
  19. 19.
    Kozopas KM, Yang T, Buchan HL, Zhou P, Craig R (1993). Mcl-1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to bcl-2. Proc Natl Acad Sci USA 90:3516–3520.PubMedGoogle Scholar
  20. 20.
    Lin EY, Orlofsky A, Berger MS, Prystowsky MB (1993). Characterization of Al, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. J Immunol 151:1979–1988.PubMedGoogle Scholar
  21. 21.
    Hengartner MO, Horvitz HR (1994). C. elegans cell survival gene ced-9 encodes a functional homolog of the mammlian proto-oncogene bcl-2. Cell 76:665–676.PubMedGoogle Scholar
  22. 22.
    Sato T, Hanada M, Bodrug S, Irie S, Iwama N, Boise LH, Thompson CB, Golemis E, Fong L, Wang H-G, Reed JC (1994). Interactions among members of the bcl-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci USA 91:9238–9242.PubMedGoogle Scholar
  23. 23.
    Croce CM, Tsujimoto Y, Erikson J, Nowell P (1984). Chromosome translocations and B cell neoplasia. Lab Invest 51:258–267.PubMedGoogle Scholar
  24. 24.
    Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides A, Arneson M (1987). Multiple recurrent genomic defects in follicular lymphoma. N Engl J Med 316:79–84.PubMedGoogle Scholar
  25. 25.
    Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979). Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res 39:3119–3128.PubMedGoogle Scholar
  26. 26.
    Eick S, Krieger G, Bolz I, Kneba M (1990). Sequence analysis of amplified t(14;18) chromosomal breakpoints in B-cell lymphomas. J Pathol 162:127–133.PubMedGoogle Scholar
  27. 27.
    Weiss LM, Warnke RA, Sklar J, Cleary ML (1987). Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med 317:1185–1189.PubMedGoogle Scholar
  28. 28.
    Tsujimoto Y, Louie E, Bashir MM, Croce CM (1988). The reciprocal partners of both the t(14;18) and t(ll;14) translocations involved in B-cell neoplasms are rearranged by the same mechanism. Oncogene 2:347–351.PubMedGoogle Scholar
  29. 29.
    Jaeger U, Putscher B, Karth GD, Knapp S, Mannhalter C, Lechner K (1993). Mechanism of the chromosomal trasnslocation t(14;18) in lymphoma: detection of a 45-Kd breakpoint binding protein. Blood 81:1833–1840.PubMedGoogle Scholar
  30. 30.
    Gribben JG, Freedman AS, Woo SD, Blake K, Shu RS, Freeman G, Longtine JA, Pinkus GS, Nadler LM (1991). All advanced stage non-Hodgkin’s lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evalutation and after treatment. Blood 78:3275–3280.PubMedGoogle Scholar
  31. 31.
    Lee M-S, Chang K-S, Cabanillas F, Freireich EJ, Trujillo JM, Stass SA (1987). Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification. Science 237:175–178.PubMedGoogle Scholar
  32. 32.
    Reed J, Tsujimoto Y, Epstein S, Cuddy M, Slabiak T, Nowell P, Croce C (1989). Regulation of bcl-2 gene expression in lymphoid cell lines containing t(14;18) or normal #18 chromosomes. Oncogene Res 4:271–282.PubMedGoogle Scholar
  33. 33.
    Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P, Korsmeyer SJ (1988). Alternative promoters and exons, somatic mutation and deregulation of the bcl-2-lg fusion gene in lymphoma. EMBO J 7:123–131.PubMedGoogle Scholar
  34. 34.
    Reed JC, Tsujimoto Y, Alpers JD, Croce CM, Nowell PC (1998). Regulation of bcl-2 proto-oncogene expression during normal human lymphocyte proliferation. Science 236:1295–1299.Google Scholar
  35. 35.
    Reed J, Haldar S, Cuddy M, Croce C, Makover D (1998). Deregulated bcl-2 expression enhances growth of a human B cell line. Oncogene 4:1123–1127.Google Scholar
  36. 36.
    Tsujimoto Y (1989). Overexpression of the human bcl-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells. Proc Natl Acad Sci USA 86:1958–1962.PubMedGoogle Scholar
  37. 37.
    Nuñez G, Seto M, Seremetis S, Ferrero D, Grignani F, Korsmeyer SJ, Dalla-Favera R (1989). Growth- and tumor-promoting effects of deregulated Bcl-2 in human B-lymphoblastoid cells. Proc Natl Acad Sci USA 86:4589–4593.PubMedGoogle Scholar
  38. 38.
    Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC (1993). bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 82:1820–1828.PubMedGoogle Scholar
  39. 39.
    Young RL, Korsmeyer SJ (1993). A negative regulatory element in the bcl-2 5′-mistranslated region inhibits expression from an upstream promoter. Mol Cell Biol 13:3686–3697.PubMedGoogle Scholar
  40. 40.
    Liu Y-J, Cairns JA, Holder MJ, Abbot SD, Jansen KU, Bonnefoy J-Y, Gordon J, MacLennan ICM (1991). Recombinant 25-kDa CD23 and interleukin la promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis. Eur J Immunol 21:1107–1114.PubMedGoogle Scholar
  41. 41.
    MacLennan ICM, Gray D (1986). Antigen-driven selection of virgin and memory B cells. Immunol Rev 91:61–66.PubMedGoogle Scholar
  42. 42.
    Sprent J (1994). T and B memory cells. Cell 76:315–322.PubMedGoogle Scholar
  43. 43.
    Liu Y-J, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan ICM (1991). Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21:1905–1910.PubMedGoogle Scholar
  44. 44.
    Pezzella F, Tse AGD, Cordell JL, Pulford KAF, Gatter KC, Mason DY (1990). Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol 137:225–232.PubMedGoogle Scholar
  45. 45.
    Horning SJ, Rosenberg SA (1984). The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Eng J Med 311:1471–1475.Google Scholar
  46. 46.
    McDonnell TJ, Nunez G, Platt FM, Hockenberry D, London L, McKearn JP, Korsmeyer SJ (1990). Deregulated bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. Mol Cell Biol 10:1901–1907.PubMedGoogle Scholar
  47. 47.
    Gauwerky CE, Hoxie J, Nowell PC, Croce CM (1988). Pre-B-cell leukemia with a t(8;14) and a t(14;18) translocation is preceded by follicular lymphoma. Oncogene 2:431–435.PubMedGoogle Scholar
  48. 48.
    De Jong D, Voetdijk BMH, Beverstock GC, van Ommen GJB, Willemze R, Kluin PM (1988). Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma. N Eng J Med 318:1373–1378.Google Scholar
  49. 49.
    McDonnell TJ, Korsmeyer SJ (1991). Progression from lymphoid typerplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18). Nature 349:254–256.PubMedGoogle Scholar
  50. 50.
    Schena M, Larsson LG, Gottardi D, Gaidano G, Carlsson M, Nilsson K, Caligaris-Cappio F (1992). Growth- and differentiation-associated expression of bcl-2 in B-chronic lymphocytic leukemia cells. Blood 79:2981–2989.PubMedGoogle Scholar
  51. 51.
    Thomas A, El Rouby S, Reed JC, Krajewski S, Potmesil M, Newcomb EW. Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: relationship of p53 gene mutation, bcl-2 and bax expression in drug resistance. Oncogene, in press.Google Scholar
  52. 52.
    Campana D, Coustan-Smith E, Manabe A, Buschle M, Raimondi SC, Behm FG, Ashmun, R, Aricó M, Biondi A, Pui C-H (1993). Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein. Blood 81:1025–1031.PubMedGoogle Scholar
  53. 53.
    Louie D, Kant J, Brooks J, Reed J (1991). Absence of t(14;18) translocation and BCL2 oncogene expression in Reed-Sternberg cells of non-Hodgkin’s disease. Am J Pathol 139:1231–1237.PubMedGoogle Scholar
  54. 54.
    Said JW, Sassoon AF, Shintaku IP, Kurtin PJ, Pinkus GS (1991). Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin’s disease. Am J Pathol 138:261–264.PubMedGoogle Scholar
  55. 55.
    Shibata D, Hue E, Weiss LM, Brynes RK, Nathwani BN (1990). Detection of specific t(14;18) chromosomal translocations in fixed tissues. Hum Pathol 21:199–203.PubMedGoogle Scholar
  56. 56.
    Stetler-Stevenson M, Crush-Stanton S, Cossman J (1990). Involvement of the bcl-2 gene in Hodgkin’s disease. J Natl Cancer Inst 82:855–858.PubMedGoogle Scholar
  57. 57.
    Said JW, Sassoon AF, Shintaku IP, Corcoran P, Nichols SW (1990). Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies. Modern Pathol 3:649–663.Google Scholar
  58. 58.
    Athan E, Chadburn A, Knowles DM (1992). The bcl-2 gene translocation is undectable in Hodgkin’s disease by Southern blot hybridization and polymerase chain reaction. Am J Pathol 141:193–201.PubMedGoogle Scholar
  59. 59.
    Claviez A, Tiemann M, Peters J, Kreipe H, Schneppenheim R, Parwaresch R (1994). The impact of EBV, proliferation rate, and Bcl-2 expression in Hodgkin’s disease in childhood. Ann Hematol 68:61–66.PubMedGoogle Scholar
  60. 60.
    Mitani S, Oka T, Aoki N, Hojo I, Ota U, Mori S (1994). Rearrangement of bcl-2 detectable in Hodgkin’s disease by polymerase chain reaction. Jpn J Cancer Res 85:1229–1232.PubMedGoogle Scholar
  61. 61.
    Limpens J, de Jong D, van Krieken JHJM, Price CGA, Young BD, van Ommen G-JJB, Kluin PM (1991). Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Oncogene 6:2271–2276.PubMedGoogle Scholar
  62. 62.
    Aster JC, Kobayashi Y, Shiota M, Mori S, Sklar J (1992). Detection of the t(14;18) at similar frequencies in hyperplastic lympoid tissues from American and Japanesse patients. Am J Pathol 141:291–299.PubMedGoogle Scholar
  63. 63.
    Liu Y, Hernandez AM, Shibata D, Cortopassi GA (1994). Bcl-2 translocation frequency rises with age in humans. Proc Natl Acad Sci USA 91:8910–8914.PubMedGoogle Scholar
  64. 64.
    Tanaka S, Louie D, Kant J, Reed J (1992). Frequent somatic mutations in translocated BCL2 genes of non-Hodgkin’s lymphoma patients. Blood 79:229–237.PubMedGoogle Scholar
  65. 65.
    Bronner M, Culin C, Reed JC, Furth EE (1994). Bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 146:20–26.Google Scholar
  66. 66.
    Colombel M, Symmans F, Gil S, O’Toole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S, Buttyan R (1993). Detection of the appoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143:390–400.PubMedGoogle Scholar
  67. 67.
    Silvestrini R, Veneroni S, Daidone MG, Benini E, Boracchi P, Mezzetti M, Di Fronzo G, Rilke F, Veronesi U (1994). The bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst 86:499–504.PubMedGoogle Scholar
  68. 68.
    Leek RD, Kaklamanis L, Pezzella F, Gatter KC, Harris AL (1994). bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer 69:135–139.PubMedGoogle Scholar
  69. 69.
    Pezzella F, Turley H, Kuzu I, Tungekar MF, Dunhill MS, Pierce CB, Harris A, Gatter KC, Mason DY (1993). bcl-2 protein in non-small-cell lung carcinoma. N Eng J Med 329:690–694.Google Scholar
  70. 70.
    Delia D, Aiello A, Soligo D, Fontanella E, Melani C, Pezzella F, Pierotti MA, Delia Porta G (1992). bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood 79:1291–1298.PubMedGoogle Scholar
  71. 71.
    Lu Z-L, Elia G, Lucas S, Thomas JA (1993). Bcl-2 proto-oncogene expression in Epstein-Barr-Virus associated nasopharyngeal carcinoma. Int J Cancer 53:29–35.PubMedGoogle Scholar
  72. 72.
    Ikegaki N, Katsumata M, Minna J, Tsujimoto Y (1994). Expression of bcl-2 in small cell lung carcinoma cells. Cancer Res 54:6–8.PubMedGoogle Scholar
  73. 73.
    Hockenberry DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ (1991). Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA 88:6961.Google Scholar
  74. 74.
    Shabaik AS, Krajewski S, Burgan A, Krajewska M, Reed JC (1994). bcl-2 proto-oncogene expression in normal, hyperplastic, and neoplastic prostate tissue. J Urologie Pathol 3:17–27.Google Scholar
  75. 75.
    Mercer WE, Shields MT, Amin M, Sauve GJ, Appella E, Romano JW, Ullrich SJ (1990). Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 87:6166–6170.PubMedGoogle Scholar
  76. 76.
    Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M (1991). Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352:345–347.PubMedGoogle Scholar
  77. 77.
    Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J (1992). Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci USA 89:4495–4499.PubMedGoogle Scholar
  78. 78.
    Lowe SW, Ruley HE, Jacks T, Houseman DE (1993). p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967.PubMedGoogle Scholar
  79. 79.
    Caelles C, Heimberg A, Karin M (1994). p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370:220–224.Google Scholar
  80. 80.
    EI-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B (1992). Definition of a consensus binding site for p53. Nature Genetics 1:45–49.Google Scholar
  81. 81.
    Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Hoffman B, Lieberman D, Reed JC (1994). Tumor suppressor p53 is a regulator of bcl-2 and bax in gene expression in vitro and in vivo. Oncogene 9:1799–1805.PubMedGoogle Scholar
  82. 82.
    Miyashita T, Harigai M, Hanada M, Reed JC (1994). Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res 54:3131–3135.PubMedGoogle Scholar
  83. 83.
    Zhan Q, Carrier F, Fornance AJ Jr (1993). Induction of cellular p53 activity by DNA-damaging agents and growth arrest. Mol Cell Biol 13:4242–4250.PubMedGoogle Scholar
  84. 84.
    Lu X, Lane DP (1993). Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell 75:765–778.PubMedGoogle Scholar
  85. 85.
    Zhan Q, Fan S, Bae I, Guillouf C, Liebermann DA, O’Connor, PM, Fornace AJ Jr (1994). Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 9:3743–3751.PubMedGoogle Scholar
  86. 86.
    Epperly MW, Santucci MA, Reed JC, Shields D, Halloran A, Greenberger JS (1994). Expression of the human bcl-2 transgene increases the radiation resistance of a hematopoietic progenitor cell line. Radiat Oncol Invest 2:77–83.Google Scholar
  87. 87.
    Fisher TC, Milner AE, Gregory CD, Jackman AL, Aherne GW, Harley JA, Dive C, Hickman JA (1993). Bcl-2 modulation of apoptosis induced by anticancer drugs: resistance to thymidylate stress is independent of classical resistance pathways. Cancer Res 53:3321–3326.PubMedGoogle Scholar
  88. 88.
    Griffiths SD, Goodhead DT, Marsden SJ, Wright EG, Krajewski S, Reed JC, Korsmeyer SJ, Greaves M (1994). Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis. J Exp Med 179:1789–1797.PubMedGoogle Scholar
  89. 89.
    Hanada M, Krajewski S, Tanaka S, Cazals-Hatem D, Spengler BA, Ross RA, Biedler JL, Reed JC (1993). Regulation of bcl-2 oncoprotein levels with differentiation of human neuroblastoma cells. Cancer Res 53:4978–4986.PubMedGoogle Scholar
  90. 90.
    Kamesaki S, Kamesaki H, Jorgensen TJ, Tanizawa A, Pommier Y, Cossman J (1993). Bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoismerase II-induced DNA strand breaks and their repair. Cancer Res 53:4251–4256.PubMedGoogle Scholar
  91. 91.
    Kitada S,Takayama S, DeRiel K, Tanaka S, Reed JC (1994). Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. Antiseense Res Dev 4:71–79.Google Scholar
  92. 92.
    Reed JC, Kitada S, Takayama S, Miyashita T (1994). Regulation of chemoresistance by the bcl-2 oncoprotein in non-Hodgkin’s lymphoma and lymphocytic leukemia cell lines. Ann Oncol 5 (Suppl 1):S61-S65.Google Scholar
  93. 93.
    Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ (1991). bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67:879–888.PubMedGoogle Scholar
  94. 94.
    Siegel RM, Katsumata M, Miyashita T, Louie DC, Greene MI, Reed JC (1992). Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice. Proc Natl Acad Sci USA 89:7003–7007.PubMedGoogle Scholar
  95. 95.
    Strasser A, Harris AW, Cory S (1991). Bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67:889–899.PubMedGoogle Scholar
  96. 96.
    Walton WI, Whysong D, O’Connor PM, Hockenbery D, Korsmeyer SJ, Kohn KW (1993). Constitutive expression of human bcl-2 modulates mitrogen mustard and camptothecin induced apoptosis. Cancer Res 53:1853–1861.PubMedGoogle Scholar
  97. 97.
    Eastman A (1990). Activation of programmed cell death by anticancer agents: cis-platin as a model system. Cancer Cells 2:275–280.PubMedGoogle Scholar
  98. 98.
    Kaufmann SH (1989). Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, campthothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res 49:5870–5878.PubMedGoogle Scholar
  99. 99.
    Kane DJ, Sarafin TA, Auton S, Hahn H, Gralla FB, Valentine JC, Ord T, Bredesen DE (1993). Bcl-2 inhibition of neural cell death: decreased generation of reactive oxygen species. Science 262:1274–1276.PubMedGoogle Scholar
  100. 100.
    Hockenbery D, Oltvai Z, Yin X-M, Milliman C, Korsmeyer SJ (1993). Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251.PubMedGoogle Scholar
  101. 101.
    Offit K, Wong G, Filippa DA, Tao Y, Chaganti RSK (1991). Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin’s lymphoma: clinical correlations. Blood 74:1508–1515.Google Scholar
  102. 102.
    Cuena R, Cruz MA, Martinez B, Garrido MC, Gatter K, Aiello A, Delia D, Giardini R, Rilke F (1994). p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time. Br J Cancer 69:337–341.PubMedGoogle Scholar
  103. 103.
    Romaguera JE, Pugh W, Luthra R, Goodacre A, Cabanillas F (1993). The clinical relevance of t(14;18)/Bcl-2 rearrangement and Del 6q in diffuse large cell lymphoma and immunoblastic lymphoma. Ann Oncol 4:51–54.PubMedGoogle Scholar
  104. 104.
    Jacobson JO, Wilkes BM, Kwiatkowski DJ, Medeiros LJ, Aisenberg AC, Harris NL (1993). Bci-2 rearrangements in De Novo diffuse large cell lymphoma. Cancer 72:231–236.PubMedGoogle Scholar
  105. 105.
    Pezzella F, Jones M, Ralfkiaer E, Ersboll J, Gatter KC, Mason DY (1992). Evaluation of bcl-2 protein expression and 14;18 translocation as prognostic markers in follicular lymphoma. Br J Cancer 65:87–89.PubMedGoogle Scholar
  106. 106.
    Castle VP, Heidelberger KP, Bromberg J, Ou X, Dole M, Nunez G (1993). Expression of the apoptosis-suppressing protein bcl-2 in neuroblastoma is associated with unfavorable histology and N-myc amplification. Am J Pathol 143:1543–1550.PubMedGoogle Scholar
  107. 107.
    Krajewski S, Chatten J, Hanada M, Womer R, Reed JC (1994). Immunohistochemical analysis of Bcl-2 oncoprotein in human neuroblastoma: correlations with tumor cell differentiation and N-myc protein. Lab Invest 35:205.Google Scholar
  108. 108.
    Wang Y, Szekely L, Okan I, Klein G, Wiman KG (1993). Wild-type p53 triggered apoptosis is inhibited by bcl-2 in a v-myc-induced T-cell lymphoma line. Oncogene 8:3427–3431.PubMedGoogle Scholar
  109. 109.
    Ryan JJ, Prochownik E, Gottlieb CA, Apel IJ, Merino R, Nuñez G, Clarke MF (1994). c-myc and bcl-2 modulates p53 function by altering p53 subcellular trafficking during the cell cycle Proc Natl Acad Sci USA 91:5878–5882.PubMedGoogle Scholar
  110. 110.
    Selvakumaran M, Lin H-K, Miyashita T, Wang H-G, krajewski S, Reed JC, Hoffman B, Liebermann D (1994). Immediate early up-regulation of bax expression by p53 but not TGFbl: a paradigm for distinct apoptotic pathways. Oncogene 9:1791–1798.PubMedGoogle Scholar
  111. 111.
    Bristow RG, Jang A, Peacock J, Chung S, Benchimol S, Hill RP (1994). Mutant p53 increases radioresistance in rat embryo fibroblasts simultaneously transfected with HPV 16-E7 and/or activated H-ras. Oncogene 9:1527–1536.PubMedGoogle Scholar
  112. 112.
    Merritt AJ, Potten CS, Kemp CJ, Hickman JA, Balmain A, Lane DP, Hall PA (1994). The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res 54:614–617.PubMedGoogle Scholar
  113. 113.
    Clarke AR, Gledhill S, Hooper ML, Bird CC, Wyllie AH (1994). p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following γ-irradiation. Oncogene 9:1767–1773.PubMedGoogle Scholar
  114. 114.
    Lowe, SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993). p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847–849.PubMedGoogle Scholar
  115. 115.
    Clarke AR, Purdie CA, Harison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH (1993). Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362: 849–852.PubMedGoogle Scholar
  116. 116.
    Sun X, Carstenen J, Zhang M, Stal O, Wingren S, Hatschek, T, Nordenskjold B (1992). Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet 340:1369–1373.PubMedGoogle Scholar
  117. 117.
    Thor AD, Moore DH II, Edgerton SM, Kawasaki ES, Reihsaus E, Lynch HT, Marcus JN, Schwartz L, Chen LC, Mayall BH (1992). Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84:845–855.PubMedGoogle Scholar
  118. 118.
    Visakorpi T, Kallioniemi O, Heikkinen A, Koivoula T, Isola J (1992). Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst 84:883–887.PubMedGoogle Scholar
  119. 119.
    Strasser A, Harris AW, Jacks T, Cory S (1994). DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by bcl-2. Cell 79:329–339.PubMedGoogle Scholar
  120. 120.
    Shen Y, Shenk T (1994). Relief of p53-mediated transcriptional repression by the adenovirus E1B 19-kDa protein or the cellular bcl-2 protein. Proc Natl Acad Sci USA 91:8940–8944.PubMedGoogle Scholar
  121. 121.
    Sabbatini P, Chiou S-K, Rao L, White E (1995). Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein. Mol Cell Biol 15:1060–1070.PubMedGoogle Scholar
  122. 122.
    Réed JC, Cuddy M, Haldar S, Croce C, Nowell P, Makover D, Bradley K (1990). BCL2-mediated tumorigenicity in a T-lymphoid cell line: synergy with C-MYC and inhibition by BCL2 antisense. Proc Natl Acad Sci USA 87:3660.PubMedGoogle Scholar
  123. 123.
    Nuñez G, London L, Hockenbery D, Alexander M, McKearn JP, Korsmeyer SJ (1990). Deregulated bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 144:3602–3610.PubMedGoogle Scholar
  124. 124.
    Borzillo GV, Endo K, Tsujimoto Y (1992). Bcl-2 confers growth and survival advantage to interleukin 7-dependent early pre-B cells which become factor independent by a multistep process in culture. Oncogene 7:869–876.PubMedGoogle Scholar
  125. 125.
    Garcia I, Martinou I, Tsujimoto Y, Martinou JC (1992). Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science 258:302–304.PubMedGoogle Scholar
  126. 126.
    Allsopp TE, Wyatt S, Paterson HF, Davies AM (1993). The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73:295–307.PubMedGoogle Scholar
  127. 127.
    Behl C, Hovey L III, Krajewski S, Schubert D, Reed JC (1993). Bcl-2 prevents killing of neuronal cell lines by L-glutamate but not by amyloid-ß peptide. BBRC 197:949–956.PubMedGoogle Scholar
  128. 128.
    Zhong L-T, Kane DJ, Bredesen DE (1993). Bcl-2 blocks glutamate toxicity in neural cell lines. Mol Brain Res 19:353–355.PubMedGoogle Scholar
  129. 129.
    Zhong IT Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH, Bredesen DE (1993). bcl-2 inhibits death of central neural cells induced by multiple agents. Proc Natl Acad Sci USA 90:4533–4537.PubMedGoogle Scholar
  130. 130.
    Selvakumaran M, Lin HK, Reed JC, Tanaka S, Liebermann DA, Hoffman B (1994). The novel differentiation-associated gene MyD 118, proto-oncogenes myb, myc, and bcl-2, and the differentiated state modulate TGFb1-induced apoptosis of myleloid leukemia cells. Mol Cell Biol 14:2352–2360.PubMedGoogle Scholar
  131. 131.
    Hennet T, Bertoni G, Richter C, Peterhans E (1993). Expression of bcl-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity. Cancer Res 53:1456–1460.PubMedGoogle Scholar
  132. 132.
    Borner C, Martinou I, Mattmann C, Irmler M, Scharer E, Martinou JC, Tschopp J (1994). The protein bcl-2a does not require membrane attachment, but two conserved domains to suppress apoptosis. J Cell Biol 126:1059–1068.PubMedGoogle Scholar
  133. 133.
    Itoh N, Tsujimoto Y, Nagata S (1993). Effect of bcl-2 on fas antigen-mediated cell death. J Immunol 151:621–627.PubMedGoogle Scholar
  134. 134.
    Vanhaesebroeck B, Reed JC, DeValck D, Miyashita Y, Tanaka S, Beyaert R, Van Roy F, Fiers W (1993). Effect of Bcl-2 proto oncogene expression on tumor necrosis on tumor necrosis factor-mediated cytotoxicity. Oncogene 8:1075–1081.PubMedGoogle Scholar
  135. 135.
    Owen-Schaub LB, Radinsky R, Kruzel E, Berry K, Yonehara S (1994). Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res 54:1580–1586.PubMedGoogle Scholar
  136. 136.
    Torigoe T, Millan JA, Takayama S, Taichman R, Miyashita T, Reed JC (1994). Bcl-2 inhibits T-cell-mediated cytolysis of leukemia cell line. Cancer Res 54:4851–4854.PubMedGoogle Scholar
  137. 137.
    Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan J, Reed JC (1995). Cloning and functional analysis of BAG-1: a novel Bcl-2 binding protein with anti-cell death activity. Cell 80:279–284.PubMedGoogle Scholar
  138. 138.
    Vaux DL, Aguila HL, Weissman IL (1992). Bcl-2 prevents death of factor-deprived cells but fails to prevent apoptosis in targets of cell mediated killing. Int Immunol 4:821–824.PubMedGoogle Scholar
  139. 139.
    Chiu VK, Walsh CM, Liu C-C, Reed JC, Clark WR. bcl-2 blocks degranulation — but not fas-based cell-mediated cytotoxicity. J Immunol 154:2023–2032, 1995.PubMedGoogle Scholar
  140. 140.
    Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J (1993). Induction of apoptosis in fibroblasts by IL-1 ß-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75:653–660.PubMedGoogle Scholar
  141. 141.
    Wang L, Miura M, Bergeron L, Zhu H, Yuan J (1994). Ich-1, and ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell 78:739–750.PubMedGoogle Scholar
  142. 142.
    Kumar S, Kinoshita M, Noda M, Copeland NG, Jenkins NA (1994). Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. Genes Dev 8:1613–1626.PubMedGoogle Scholar
  143. 143.
    Tsujimoto Y (1989). Stress-resistance conferred by high level of bcl-2a protein in human B lymphoblastoid cell. Oncogene 4:1331–1336.PubMedGoogle Scholar
  144. 144.
    Levine B, Huang Q, Isaacs JT, Reed JC, Griffin DE, Hardwick JM (1993). Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361:739–742.PubMedGoogle Scholar
  145. 145.
    Yamada T, Yamaoka S, Goto T, Nakai M, Tsujimoto Y, Hatanaka M (1994). The human T-cell leukemia virus type I Tax protein induces apoptosis which is blocked by the bcl-2 protein. J Virol 68:3374–3379PubMedGoogle Scholar
  146. 146.
    Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S (1992). The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kda and bcl-2 proteins. Proc Natl Acad Sci USA 89:7742–7746.PubMedGoogle Scholar
  147. 147.
    Bissonnette RP, Echeverri F, Mahboubi A, Green DR (1992). Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359:552–554.PubMedGoogle Scholar
  148. 148.
    Fanidi A, Harrington EA, Evan GI (1992). Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature 359:554–556.PubMedGoogle Scholar
  149. 149.
    Wang H-G, Millan JA, Cox AD, Der CJ, Rapp UR, Beck T, Reed JC (1995). R-Ras promotes apoptosis caused by growth factor deprivation via a bcl-2 suppressible mechanism. J Cell Biol 129:1103–1114, 1995.Google Scholar
  150. 150.
    Asken DS, Ashmen RA, Simmons BC, Cleveland JL (1991). Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922.Google Scholar
  151. 151.
    Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC (1992). Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119–128.PubMedGoogle Scholar
  152. 152.
    Alnemri ES, Robertson NM, Fernandes TF, Croce CM, Litwack G (1992). Overexpressed full-length human Bcl-2 extends the survival of baculovirus-infected Sf9 insect cells. Proc Natl Acad Sci USA 89:7295–7299.PubMedGoogle Scholar
  153. 153.
    Vaux DL, Weissman IL, Kim SK (1992). Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science 258:1955–1957.PubMedGoogle Scholar
  154. 154.
    Kitada S, Miyashita T, Tanaka S, Reed JC (1993). Investigations of antisense oligonucleotides targeted against bcl-2 RNAs. Antisense Res Deve 3:157–169.Google Scholar
  155. 155.
    Nakayama KI, Nakayama K, Negishi I, Kuida K, Shinkai Y, Louie MC, Fields LE, Lucas PJ, Stewart V, Alt FW, Loh DY (1993). Disappearance of the lymphoid system in bcl-2 homozygous mutant chimeric mice. Science 261:1584–1588.PubMedGoogle Scholar
  156. 156.
    Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993). Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229–240.PubMedGoogle Scholar
  157. 157.
    Cuende E, Ales-Martinez JE, Ding L, Gonzalez-Garcia M, Martinez-A C, Nunez G (1993). Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells. EMBO J 12:1555–1560.PubMedGoogle Scholar
  158. 158.
    Makover D, Cuddy M, Bradley K, Alpers J, Sukhatme V, Reed J (1989). Phorbol ester-mediated inhibition of growth and regulation of proto-oncogene expression in the human T cell leukemia line JURKAT. Oncogene 6:455–460.Google Scholar
  159. 159.
    Chen-Levy Z, Cleary ML (1990). Membrane topology of the Bcl-2 proto-oncogenic protein demonstrated in vitro. J Biol Chem 265:4929–4933.PubMedGoogle Scholar
  160. 160.
    Monaghan P, Robertson D, Andrew T, Amos S, Dyer MJS, Mason DY, Greaves MF (1992). Ultrastructural localization of bcl-2 protein. J Histochem Cytochem 40:1819–1825.PubMedGoogle Scholar
  161. 161.
    Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC (1993). Investigations of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res 53:4701–4714.PubMedGoogle Scholar
  162. 162.
    de Jong D, Prins FA, Mason DY, Reed JC, van Ommen GB, Kluin PM (1994). Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. Cancer Res 54:256–260.PubMedGoogle Scholar
  163. 163.
    Lithgow T, van Driel R, Bertram JF, Strasser A (1994). The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the other mitochondrial membrane. Cell-Growth Differ 3:411–417.Google Scholar
  164. 164.
    Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y (1994). Multiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res 54:2468–2471.PubMedGoogle Scholar
  165. 165.
    Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC (1993). Apoptosis and bcl-2 protein in cells without mitochondrial DNA. Nature 361:365–368.PubMedGoogle Scholar
  166. 166.
    Meikrantz W, Gisselbrecht S, Tarn SW, Schlegel R (1994). Activation of cyclin A-dependent protein kinases during apoptosis. Proc Natl Acad Sci USA 91:3754–3758.PubMedGoogle Scholar
  167. 167.
    Chiou SK, Rao L, White E (1994). Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol 14:2556–2563.PubMedGoogle Scholar
  168. 168.
    Shen Y, Shenk T (1994). Relief of p53-mediated transcriptional repression by the adenovirus E1B 19-kDa protein or the cellular Bcl-2 protein. Proc Natl Acad Sci USA 91:8940–8944.PubMedGoogle Scholar
  169. 169.
    Jacobson MD, Burne JF, Raff MC (1994). Programmed cell death and Bcl-2 protection in the absence of a nucleus. EMBO J 13:1899–1910.PubMedGoogle Scholar
  170. 170.
    Baffy G, Miyashita T, Williamson JR, Reed JC (1993). Apoptosis induced by withdrawal of Interleukin-3 IL-3] from an IL-3-dependent hematopoietic cell line associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J Biol Chem 268:6511–6519.PubMedGoogle Scholar
  171. 171.
    Lam M, Dubyak G, Chen L, Nuñez G, Miesfeld RL, Distelhorst CW (1994). Evidence that bcl-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. PNAS 91:6569–6573.PubMedGoogle Scholar
  172. 172.
    Lam M, Dubyak G, Distelhorst CW (1993). Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells. Mol Endocrinol 7:686–693.PubMedGoogle Scholar
  173. 173.
    Dowd DR, MacDonald PN, Komm BS, Haussler MR, Miesfeld RL (1992). Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes. Mol Endocrinol 6:1843–1848.PubMedGoogle Scholar
  174. 174.
    Newmeyer D, Farschon DM, Reed JC (1994). Cell-free apoptosis in Xenopus egg extracts: by Bcl-2 inhibits a latant cytoplasmic phase. Cell 79:353–364.PubMedGoogle Scholar
  175. 175.
    Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T, Kitamura Y, Kondoh H, Tsujimoto Y (1995). Bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, distorted intestine and hair hypopigmentation. Cancer Res 55:354–359.PubMedGoogle Scholar
  176. 176.
    Neilan JG, Lu A, Afonso CL, Kutish GF, Sussman MD, Rock DL (1993). An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr Virus gene BHRF1. J Virology 67:4391–4394.PubMedGoogle Scholar
  177. 177.
    Yang E, Zha J, Jockei J, Boise LH, Thompson CB, Korsmeyer SJ (1995). Bad: a heterodimeric partner for Bcl-XL and Bcl-2, displaces bax and promotes cell death. Cell 80:285–291.PubMedGoogle Scholar
  178. 178.
    Farrow SN, White JHM, Martinou I, Raven T, Pun K-T, Grinham CJ, Martinou J-C, Brown R (1995). Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature 374:731–733.PubMedGoogle Scholar
  179. 179.
    Chittenden T, Harrington EA, O’Connor R, Flemington C, Lutz RJ, Evan Gl, Guild BC (1995). Induction of apoptosis by the Bcl-2 homologue Bak. Nature 374:733–736.PubMedGoogle Scholar
  180. 180.
    Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Ubansky SR, Tomei LD, Barr PJ (1995). Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374: 736–739.PubMedGoogle Scholar
  181. 181.
    Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A (1993). Epstein-Barr virus-coded BHRF1 protein, a viral homologue of bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci USA 90:8479–8483.PubMedGoogle Scholar
  182. 182.
    Takayama S, Cazals-Hatem DL, Kitada S, Tanaka S, Miyashita T, Hovey LR, Huen D, Rickinson A, Veerapandian P, Krajewski S, Saito K, Reed JC (1994). Evolutionary conservation of function among mammalian, avian, and viral homologs of the bcl-2 oncoprotein: structure-function implications. DNA Cell Biol 13:679–692.PubMedGoogle Scholar
  183. 183.
    White E, Sabbatini P, Debbas M, Wold WSM, Kusher DI, Gooding LR (1992). The 19-kilodalton adenovirus E1B transfforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor-α. Mol Cell Biol 12:2570–2580.PubMedGoogle Scholar
  184. 184.
    Sato T, Irie S, Krajewski S, Reed JC (1994). Cloning and sequencing of cDNA encoding rat bcl-2 protein. Gene 140:291–292.PubMedGoogle Scholar
  185. 185.
    González-Garcia M, Pérez-Ballestero R, Ding L, Duan L, Boise LH, Thompson CB, Núñez G (1994). bcl-XL is the major bcl-X raRNA form expressed during murine development and its product localizes to mitochondria. Development 120:3033–3042.PubMedGoogle Scholar
  186. 186.
    Tanaka S, Saito K, Reed JC (1993). Structure-function analysis of the apoptosis-suppressing bcl-2 oncoprotein: substitution of a heterologous transmembrane domain restores function to truncated Bcl-2 proteins. J Biol Chem 268:10920–10926.PubMedGoogle Scholar
  187. 187.
    Nguyen M, Branton PE, Walton PA, Oltvai ZN, Korsmeyer SJ, Shore GC (1994). Role of membrane anchor domain of bcl-2 in suppression of apoptosis caused by E1B-defective adenovirus. J Biol Chem 269:16521–16524.PubMedGoogle Scholar
  188. 188.
    Frisch SM, Francis H (1994). Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626.PubMedGoogle Scholar
  189. 189.
    Yang T, Kozopas KM, Craig RW (1995). The intracellular distribution and pattern of expresion of Mcl-1 overlap with, but are not identical to, those of Bcl-2. J Cell Biol 128:1173–1184.PubMedGoogle Scholar
  190. 190.
    Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang H-G, Reed JC (1994). Immuno-histochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol 145:1323–1333.PubMedGoogle Scholar
  191. 191.
    Krajewski S, Bodrug S, Gascoyn R, Berean K, Krajewska M, Reed JC (1994). Immunohis-tochemical analysis of mcl-1 and bcl-2 proteins in normal and neoplastic lymph nodes. Amer J Pathol 145:515–525.Google Scholar
  192. 192.
    Krajewski S, Krajewska M, Shabaik A, Wang H-G, Irie S, Fong L, Reed JC (1994). Immu-nohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res 54:5501–5507.PubMedGoogle Scholar
  193. 193.
    Hickish T, Robertson D, Clarke P, Hill M, di Stefano F, Clarke C, Cunningham D (1994). Ultrastructural localization of BHRF1: an Epstein-Barr virus gene product which has homology with bcl-2. Cancer Res 54:2808–2811.PubMedGoogle Scholar
  194. 194.
    White E, Cipriani R (1989). Specific disruption of intermediate filaments and the nuclear lamina by the 19-kDa product of the adenovirus E1B oncogene. Proc Natl Acad Sci USA 86:9886–9890.PubMedGoogle Scholar
  195. 195.
    Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, Korsmeyer SJ (1995). Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci USA 92:7834–7838.PubMedGoogle Scholar
  196. 196.
    Yang E, Zha J, Jockei J, Boise LH, Thompson CB, Korsmeyer SJ (1995). Bad: a heterodimeric partner for Bcl-XL and Bcl-2, displaces bax and promotes cell death. Cell 80:285–291.PubMedGoogle Scholar
  197. 197.
    Yin X-M, Oltvai ZN, Korsmeyer SJ (1994). BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369:321–323.PubMedGoogle Scholar
  198. 198.
    Bodrug SE, Aimé-Sempé C, Sato T, Krajewski S, Hanada M, Reed JC (1995). Biochemical and functional comparisons of Mcl-1 and Bcl-2 proteins: evidence for a novel mechanism of regulating Bcl-2 family protein function. Cell Death Differ 2:173–182.PubMedGoogle Scholar
  199. 199.
    Liu Y, Hernandez AM, Shibata D, Cortopassi GA (1994). Bcl-2 translocation frequency rises with age in humans. Proc Natl Acad Sci USA 91:8910–8914.PubMedGoogle Scholar
  200. 200.
    Borner C, Martinou I, Mattmann C, Irmler M, Scharer E, Martinou J-C, Tschopp J (1994). The protein bcl-2alpha does not require membrane attachment, but two conserved domains to suppress apoptosis. J Cell Biol 126:1059–1068.PubMedGoogle Scholar
  201. 201.
    Hanada M, Aimé-Sempé C, Sato T, Reed JC (1995). Structure-function analysis of bcl-2 protein: identification of conserved domains important for homodimerization with bcl-2 and heterodimerization with bax. J Biol Chem 270:11962–11969.PubMedGoogle Scholar
  202. 202.
    Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, Rickinson A (1991). Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115.PubMedGoogle Scholar
  203. 203.
    Finke J, Fritzen R, Ternes P, Trivedi P, Bross KJ, Lange W, Mertelsmann R, Dolken G (1992). Expression of bcl-2 in Burkitt’s lymphoma cell lines: induction by latent Epstein-Barr virus genes. Blood 80:459–469.PubMedGoogle Scholar
  204. 204.
    Rowe M, Peng-Pilon M, Huen DS, Hardy R, Croom-Carter D, Lundgren E, Rickinson AB (1994). Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers. J Virol 68:5602–5612.PubMedGoogle Scholar
  205. 205.
    Fernandez MJ, Bischoff JR (1993). Bcl-2 associates with the ras-related protein R-ras p23. Nature 366:274–275.Google Scholar
  206. 206.
    Wang H-G, Miyashita T, Takayama S, Sato T, Torigoe T, Krajewski S, Tanaka S, Hovey L III, Troppmair J, Rapp UR, Reed JC (1994). Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene 9:2751–2756.PubMedGoogle Scholar
  207. 207.
    Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D’Sa-Eipper C, Chinnadurai G. Adenovirus E1B 19 kDa and bcl-2 proteins interact with a common set of cellular proteins. Cell 79:341–351.Google Scholar
  208. 208.
    Cox AD, Brtva TR, Lowe DG, Der CJ (1994). R-ras induces malignant, but not morphologic, transformation of NIH 3T3 cells. Oncogene 9:3281–3288.PubMedGoogle Scholar
  209. 208a.
    Gottschalk AR, Boise LH, Thompson CB, Quintáns J (1994). Identification of immunosup-pressant-induced apoptosis in a murine B-cell line and its prevention by bcl-X but not bcl-2. Proc Natl Acad Sci USA 91:7350–7354.PubMedGoogle Scholar
  210. 209.
    Rey I, Taylor-Harris P, van Erp H, Hall A (1994). R-ras interacts with rasGAP, neurofibromin and c-raf but does not regulate cell growth or differentiation. Oncogene 9:685–692.PubMedGoogle Scholar
  211. 210.
    Spaargaren M, Martin GA, McCormick F, Fernandez-Sarabia MJ, Bischoff JR (1994). The Ras-related protein R-ras interacts directly with Raf-1 in a GTP-dependent manner. Biochem J 300:303–307.PubMedGoogle Scholar
  212. 211.
    Wang H-G, Millan JA, Cox AD, Der CJ, Rapp UR, Beck T, Zha H, Reed JC (1995). R-ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism. J Cell Biol 129:1103–1114.PubMedGoogle Scholar
  213. 212.
    Kocache MM, Pearson GR (1990). Protein kinase activity associated with a cell cycle regulated, membrane-bound Epstein-Barr virus induced early antigen. Intervirology 31:1–13.PubMedGoogle Scholar
  214. 213.
    Krajewski S, Krajewska M, Shabaik A, Wang H-G, Irie S, Fong L, Reed JC (1994). Immu-nohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res 54:5501–5507.PubMedGoogle Scholar
  215. 214.
    Krajewski S, Bodrug S, Krajewska M, Shabaik A, Gascoyne R, Berean K, Reed JC (1995). Immunohistochemical analysis of Mcl-1 protein in human tissues: differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. Am J Pathol.Google Scholar
  216. 214a.
    Datta R, Manome Y, Taneja N, Boise LH, Weichselbaum R, Thompson CB, Slapak CA, Kufe D (1995). Overexpression of Bcl-XL by cytoxic drug exposure confers resistance to ionizing radiation-induced internucleosomal DNA fragmentation. Cell Growth Differ 6:363–370.PubMedGoogle Scholar
  217. 215.
    LeBrun DP, Warnke RA, Cleary ML (1993). Expression of bcl-2 in fetal tissues suggests a role in morphogenesis. Am J Pathol 142:743–753.PubMedGoogle Scholar
  218. 215a.
    Kühl J-S, Krajewski S, Durán GE, Reed JC, Sikic B (submitted). A spontaneously resistant variant of murine P388 leukemia with broad cross-resistance to cytotoxins and overexpression of the long form of the Bcl-X protein.Google Scholar
  219. 216.
    Lu Q-L, Pousom R, Wong L, Hanby AM (1993). bcl-2 expression in adult and embryonic non-haematopoietic tissues. J Pathol 169:431–437.Google Scholar
  220. 216a.
    Perego P, Miyashita T, Delia D, Reed JC, Zunino F (1994). Association between cisplatin-resistant mutation of p53 gene and reduced Bax expression in ovarian carcinoma cell systems. Cancer Res 56:556–562.Google Scholar
  221. 217.
    Novack DV, Korsmeyer SJ (1994). Bcl-2 protein expression during murine development. Am J Pathol 145:61–73.PubMedGoogle Scholar
  222. 217a.
    Schlaifer D, March M, Krajewski S, Reed JC, Brousset P (1995). High expression of the Bcl-X gene in Reed-Sternberg cells of Hodgkin’s disease. Blood 85:2671–2674.PubMedGoogle Scholar
  223. 218.
    Krajewski S, Blomqvist C, Franssila K, Krajewska M, Wasenius V-M, Niskanen E (1995). Reduced expression of pro-apoptotic gene Bax is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 55:4471–4478.PubMedGoogle Scholar
  224. 219.
    Miyashita T, Reed JC (1995). Tumor suppressor p53 is a direct transcriptional activator of human bax gene. Cell 80:293–299.PubMedGoogle Scholar
  225. 220.
    Gottlieb E, Haffner R, von Rüden T, Wagner EF, Oren M (1994). Down-regulation of wild-type p53 activity interferes with apoptosis of IL-3-dependent hematopoietic cells following IL-3 withdrawal. EMBO J 13:1368–1374.PubMedGoogle Scholar
  226. 221.
    Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW, Taniguchi T (1994). Cellular commitment to oncogene -induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell 77:829–839.PubMedGoogle Scholar
  227. 222.
    Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RSK, Dalla-Favera R (1993). p53 mutations are associated with histologic transformation of follicular lymphoma. Blood 82:2289–2295.PubMedGoogle Scholar
  228. 223.
    Sander CA, Yano T, Clark HM, Harris C, Longo DL, Jaffe ES, Raffeid M (1993). p53 mutation is associated with progression in follicular lymphomas. Blood 82:1994–2004.PubMedGoogle Scholar
  229. 224.
    Otani H, Erdos M, Leonard WJ (1993). Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line. J Biol Chem 268:22733–22736.PubMedGoogle Scholar
  230. 225.
    Levy Y, Brouet J-C (1994). Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest 93:424–428.PubMedGoogle Scholar
  231. 226.
    Fernandez A, Marin MC, McDonnel T, Ananthaswamy HN (1994). Differential sensitivity of normal and Ha-ras-transformed C3H mouse embryo fibroblasts to tumor necrosis factor: induction of bcl-2, c-myc, and manganese superoxide dismutase in resistant cells. Oncogene 9:2009–2017.PubMedGoogle Scholar
  232. 227.
    Carson WE, Haider S, Baiocchi RA, Crose CM, Caligiuri MA (1994). The c-kit ligand supresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci USA 91:7553–7557.PubMedGoogle Scholar
  233. 228.
    Prehn J, Bindokas V, Maracilli C, Krajewski S, Reed JC, Millan R Transforming growth factor-ßs (TGF-ß) have wide-ranging neuroprotective properties on rat hippocampal neurones. Proc Natl Acad Sci USA 91:12599–12603.Google Scholar
  234. 229.
    Kenny JJ, Fischer RT, Lustig A, Dintzis H, Katsumata M, Greene MI, Reed JC, Longo DL (submitted). Bcl-2 alters the antigen-driven selection of B cells in μk but not in μ-only Xid transgenic mice.Google Scholar
  235. 230.
    Campos L, Sabido O, Roualult J-P, Guyayat D (1994). Effects of Bcl-2 antisense oligodeoxynucleotides on in vitro proliferation and survival of normal marrow progenitors and leukemic cells. Blood 84:595–600.PubMedGoogle Scholar
  236. 231.
    Cotter FE, Johnson P, Hall P, Pocock C, Mahdi NA, Cowell JK, Morgan G (1994). Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogene 9:3049–3055.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1996

Authors and Affiliations

  • John C. Reed
  • Toshiyuki Miyashita
  • Stanislaw Krajewski
  • Shinichi Takayama
  • Christine Aime-Sempe
  • Shinichi Kitada
  • Takaaki Sato
  • Hong-Gang Wang
  • Masayoshi Harigai
  • Motoi Hanada
  • Maryla Krajewska
  • Kristine Kochel
  • Juan Millan
  • Hiroko Kobayashi

There are no affiliations available

Personalised recommendations