Retinoblastoma gene in malignancy

  • Lance C. Pagliaro
Part of the Cancer Treatment and Research book series (CTAR, volume 84)


The central importance of genetic damage in the development of tumors was suspected prior to the advent of molecular biology because chemical carcinogens were noted to be potent mutagens as well [1]. Hereditary cancer syndromes provided further evidence of a genetic basis for carcinogenesis [2]. The identities of the genes involved remained unknown until the 1970s, when the study of animal RNA tumor viruses led to the discovery of several vertebrate genes that could acquire transforming properties through mutation [3,4]. The consequences of these genetic alterations are now beginning to be understood. Knudson proposed that at least two separate mutational events are required, based on his observations of hereditary and nonhereditary retinoblastoma tumors in children [5]. According to his two-hit hypothesis, sporadic tumor formation requires the independent occurrence of both mutations within the same cell, whereas in individuals who inherit one mutation in the germline, only the second mutation is required. Using the estimated frequency of spontaneous mutation, Knudson showed that the hypothesis correctly predicts multiple bilateral tumors in patients with the inherited retinoblastoma susceptibility trait, and solitary unilateral tumors in nonhereditary cases.


Retinoblastoma Gene Retinal Progenitor Cell Retinoblastoma Gene Product Acute Myelogenous Leukemia Blast Retinoblastoma Susceptibility Gene 
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  1. 1.
    McCann J, Choi E, Yamasaki E, Ames BN (1975). Detection of carcinogens as mutagens in the Salmonella/microsome test. Proc Natl Acad Sci USA 72:5135–5139.PubMedCrossRefGoogle Scholar
  2. 2.
    Knudson AG (1985). Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 45:1437–1443.PubMedGoogle Scholar
  3. 3.
    Bishop JM (1985). Viral oncogenes. Cell 42:23–38.PubMedCrossRefGoogle Scholar
  4. 4.
    Weinberg RA (1994). Oncogenes and tumor suppressor genes. CA Cancer J Clin 44:160–170.PubMedCrossRefGoogle Scholar
  5. 5.
    Knudson AG (1971). Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823.PubMedCrossRefGoogle Scholar
  6. 6.
    Lee W-H, Bookstein RE, Lee EY-HP (1990). Molecular biology of the human retinoblastoma gene. Immunol Ser 51:169–200.PubMedGoogle Scholar
  7. 7.
    Klein G (1993). Genes that suppress cancer. FASEB J 7:821–825.PubMedGoogle Scholar
  8. 8.
    Yunis JJ, Ramsay N (1978). Retinoblastoma and subband deletion of chromosome 13. Am J Dis Child 132:161–163.PubMedGoogle Scholar
  9. 9.
    Godbout R, Dryja T, Squire J, Gallie BL, Phillips RA (1983). Somatic inactivation of genes on chromosome 13 is a common event in both hereditary and nonhereditary retinoblastoma tumors. Nature 304:451–453.PubMedCrossRefGoogle Scholar
  10. 10.
    Lee W-H, Bookstein R, Hong F, Young L-J, Shew J-Y, Lee EY-HP (1987). Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235:1394–1399.PubMedCrossRefGoogle Scholar
  11. 11.
    Dunn JM, Phillips RA, Becker AJ, Gallie BL (1988). Identification of germline and somatic mutations affecting the retinoblastoma gene. Science 241:1797–1800.PubMedCrossRefGoogle Scholar
  12. 12.
    Hamel PA, Phillips RA, Muncaster M, Gallie BL (1993). Speculations on the roles of RB1 in tissue-specific differentiation, tumor initiation, and tumor progression. FASEB J 7:846–854.PubMedGoogle Scholar
  13. 13.
    Fearon ER, Vogelstein B (1990). A genetic model for colorectal tumorigenesis. Cell 61:759–767.PubMedCrossRefGoogle Scholar
  14. 14.
    Hong FD, Huang H-JS, To H, Young L-JS, Oro A, Bookstein R, Lee EY-HP, Lee W-H (1989). Structure of the human retinoblastoma gene. Proc Natl Acad Sci USA 86:5502–5506.PubMedCrossRefGoogle Scholar
  15. 15.
    Bernards R, Schackleford GM, Gerber MR, Horowitz JM, Friend SH, Schartl M, Bogenmann E, Rapaport JM, McGee T, Dryja TP, Weinberg RA (1989). Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein. Proc Natl Acad Sci USA 86:6474–6478.PubMedCrossRefGoogle Scholar
  16. 16.
    Zacksenhaus E, Bremner R, Jiang Z, Gill RM, Muncaster M, Sopta M, Phillips RA, Gallie BL (1993). Unraveling the function of the retinoblastoma gene. Adv Cancer Res 61:115–141.PubMedCrossRefGoogle Scholar
  17. 17.
    Martinez JC, Piris MA, Sanchez-Beato M, Villuendas R, Orradre JL, Algara P, Sanchez-Verde L, Martinez P (1993). Retinoblastoma (Rb) gene product expression in lymphomas. Correlation with Ki67 growth fraction. J Pathol 169:405–412.PubMedCrossRefGoogle Scholar
  18. 18.
    Slack RS, Hamel PA, Bladon TS, Gill RM, McBurney MW (1993). Regulated expression of the retinoblastoma gene in differentiating embryonal carcinoma cells. Oncogene 8:1585–1591.PubMedGoogle Scholar
  19. 19.
    Yen A, Varvayanis S, Platko JD (1993). 12-O-tetradecanoylphorbol-13-acetate and staurosporine induce increased retinoblastoma tumor suppressor gene expression with mega-karyocytic differentiation of leukemic cells. Cancer Res 53:3085–3091.PubMedGoogle Scholar
  20. 20.
    Shiio Y, Yamamoto T, Yamaguchi N (1992). Negative regulation of Rb expression by the p53 gene product. Proc Natl Acad Sci USA 89:5206–5210.PubMedCrossRefGoogle Scholar
  21. 21.
    Hamel PA, Gill RM, Phillips RA, Gallie BL (1992). Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene. Mol Cell Biol 12:3431–3438.PubMedGoogle Scholar
  22. 22.
    Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Bogger A, Gedde-Dahl T, Cavenee WK (1985). Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA 82:6216–6220.PubMedCrossRefGoogle Scholar
  23. 23.
    Horowitz JM, Park S-H, Bogenmann E, Cheng J-C, Yandell DW, Kaye FJ, Minna JD, Dryja TP, Weinberg RA (1990). Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc Natl Acad Sci USA 87:2775–2779.PubMedCrossRefGoogle Scholar
  24. 24.
    Wadayama B, Toguchida J, Shimizu T, Ishizaki K, Sasaki MS, Kotoura Y, Yamamuro T (1994). Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res 54:3042–3048.PubMedGoogle Scholar
  25. 25.
    Ishikawa J, Xu H-J, Hu S-X, Yandell DW, Maeda S, Kamindono S, Benedict WF, Takahashi R (1991). Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas. Cancer Res 51:5736–5743.PubMedGoogle Scholar
  26. 26.
    Hensel CH, Hsieh C-L, Gazdar AF, Johnson BE, Sakaguchi AY, Naylor SL, Lee W-H, Lee EY-HP (1990). Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer. Cancer Res 50:3067–3072.PubMedGoogle Scholar
  27. 27.
    Xu H-J, Hu S-X, Cagle PT, Moore GE, Benedict WF (1991). Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas. Cancer Res 51:2735–2739.PubMedGoogle Scholar
  28. 28.
    T’ang A, Varley JM, Chakraborty S, Murphree AL, Fung Y-KT (1988). Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science 242:263–266.PubMedCrossRefGoogle Scholar
  29. 29.
    Kim TM, Benedict WF, Xu H-J, HU S-X, Gosewehr J, Velicescu M, Yin E, Zheng J, D’Ablaing G, Dubeau L (1994). Loss of heterozygosity on chromosome 13 is common only in the biologically more aggressive subtypes of ovarian epithelial tumors and is associated with normal retinoblastoma gene expression. Cancer Res 54:605–609.PubMedGoogle Scholar
  30. 30.
    Murakami Y, Hayashi K, Hirohashi S, Sekiya T (1991). Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res 51:5520–5525.PubMedGoogle Scholar
  31. 31.
    Cryns VL, Thor A, Xu H-J, Hu S-X, Wierman ME, Vickery AL, Benedict WF, Arnold A (1994). Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med 330:757–761.PubMedCrossRefGoogle Scholar
  32. 32.
    Ruggeri B, Zhang S-Y, Caamano J, DiRado M, Flynn SD, Klein-Szanto AJP (1992). Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. Oncogene 7:1503–1511.PubMedGoogle Scholar
  33. 33.
    Cance WG, Brennan MF, Dudas ME, Huang C-M, Cordon-Cardo C (1990). Altered expression of the retinoblastoma gene product in human sarcomas. N Engl J Med 323:1457–1462.PubMedCrossRefGoogle Scholar
  34. 34.
    Hamel W, Westphal M, Shepard HM (1993). Loss in expression of the retinoblastoma gene product in human gliomas is associated with advanced disease. J Neuro-Oncol 16:159–165.CrossRefGoogle Scholar
  35. 35.
    Logothetis CJ, Xu H-J, Ro JY, Hu S-X, Sahin A, Ordonez N, Benedict WF (1992). Altered expression of retinoblastoma protein and known prognostic variables in locally advanced bladder cancer. J Natl Cancer Inst 84:1256–1261.PubMedCrossRefGoogle Scholar
  36. 36.
    Phillips RA, Gill RM, Zacksenhaus E, Bremner R, Jiang Z, Sopta M, Gallie BL, Hamel PA (1992). Why don’t germline mutations in RB1 predispose to leukemia? Current Topics Microbiol Immunol 182:487–491.Google Scholar
  37. 37.
    Morris CM, Cochrane JM, Benjes SM, Crossen PE, Fitzgerald PH (1991). Molecular definition of interstitial deletions of chromosome 13 in leukemic cells. Genes Chrom Cancer 3:455–460.PubMedCrossRefGoogle Scholar
  38. 38.
    Chen Y-C, Chen P-J, Yeh S-H, Tien H-F, Wang C-H, Tang J-L, Hong R-L (1990). Deletion of the human retinoblstoma gene in primary leukemia. Blood 76:2060–2064.PubMedGoogle Scholar
  39. 39.
    Ahuja HG, Jat PS, Foti A, Bar-Eli M, Cline MJ (1991). Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia. Blood 78:3259–3268.PubMedGoogle Scholar
  40. 40.
    Zhou Y-M, Bradbury D, Russell N (1994). Decreased retinoblastoma protein expression in acute myeloblastic leukaemia is associated with the autonomous proliferation of clonogenic blasts. Br J Haematol 86:533–539.CrossRefGoogle Scholar
  41. 41.
    Ginsberg AM, Raffeld M, Cossman J (1992). Mutations of the retinoblastoma gene in human lymphoid neoplasms. Leuk Lymphoma 7:359–362.PubMedCrossRefGoogle Scholar
  42. 42.
    Liu Y, Soderhall S, Heyman M, Grander D, Brondum-Nielsen K, Einhorn S (1994). Multiple genetic events involving RB1 gene deletion and amplification of chromosome 21 in a case of acute lymphocytic leukemia. Genes Chrom Cancer 9:72–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhou M, Zaki SR, Ragab AH, Findley HW (1993). Frequent alteration of Rb tumor-suppressor gene in childhood acute lymphoblastic leukemia. Proc Am Assoc Cancer Res 34:104 (abstract).Google Scholar
  44. 44.
    Stilgenbauer S, Dohner H, Bulgay-Morschel M, Weitz S, Bentz M, Lichter P (1993). High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics. Blood 81:2118–2124.PubMedGoogle Scholar
  45. 45.
    Juliusson G, Oscier DG, Fitchett M, Ross FM, Stockdill G, Mackie MJ, Parker AC, Castoldi GL, Cuneo A, Knuutila S, Elonen E, Gahrton G (1990). Prognostic subgroups in B-cell CLL defined by specific chromosomal abnormalities. N Engl J Med 323:720.PubMedCrossRefGoogle Scholar
  46. 46.
    Weide R, Tiemann M, Pfluger K-H, Koppler H, Parvizl B, Wacker H-H, Kreipe H-H, Havemann K, Parwaresch MR (1994). Altered expression of the retinoblastoma gene product in human high grade non-Hodgkin’s lymphomas. Leukemia 8:97–101.PubMedGoogle Scholar
  47. 47.
    Corradini P, Inghirami G, Astolfi M, Ladetto M, Voena C, Ballerini P, Gu W, Nilsson K, Knowles DM, Boccadoro M, Pileri A, Dalla-Favera R (1994). Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias. Leukemia 8:758–767.PubMedGoogle Scholar
  48. 48.
    Dao DD, Sawyer JR, Epstein J, Hoover RG, Barlogie B, Tricot G (1994). Deletion of the retinoblastoma gene in multiple myeloma. Leukemia 8:1280–1284.PubMedGoogle Scholar
  49. 49.
    Lee W-H, Shew J-Y, Hong F, Sery T, Donoso LA, Young LJ, Bookstein R, Lee EY-HP (1987). The retinoblastoma susceptibility gene product is a nuclear phosphoprotein associated with DNA binding activity. Nature 329:642–645.PubMedCrossRefGoogle Scholar
  50. 50.
    Welch PJ, Wang YJ (1993). A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-able tyrosine kinase in the cell cycle. Cell 75:779–790.PubMedCrossRefGoogle Scholar
  51. 51.
    Zacksenhaus E, Bremner R, Phillips RA, Gallie BL (1993). A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity. Mol Cell Biol 13:4588–4599.PubMedGoogle Scholar
  52. 52.
    Lee W-H, Hollingsworth RE, Qian Y-W, Chen P-L, Hong F, Lee EY-HP (1991). RB protein as a cellular ‘corral’ for growth-promoting proteins. Cold Spring Harbor Symp Quant Biol 56:211–217.PubMedGoogle Scholar
  53. 53.
    Ludlow JW, deCaprio JA, Huang CM, Lee W-H, Paucha E, Livingston DM (1989). SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. Cell 56:57–65.PubMedCrossRefGoogle Scholar
  54. 54.
    Ewen ME, Sluss HK, Whitehouse LL, Livingston DM (1993). TGFβ inhibition of cdk4 synthesis is linked to cell cycle arrest. Cell 74:1009–1020.PubMedCrossRefGoogle Scholar
  55. 55.
    Kato JY, Sherr CJ (1993). Inhibition of granulocyte differentiation by Gl cyclins D2 and D3 but not D1. Proc Natl Acad Sci USA 90:11513–11517.PubMedCrossRefGoogle Scholar
  56. 56.
    Goodrich DW, Lee W-H (1993). Molecular characterization of the retinoblastoma susceptibility gene. Biochim Biophys Acta 1155:43–61.PubMedGoogle Scholar
  57. 57.
    DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang C-M, Lee W-H, Marsillo E, Paucha E, Livingston DM (1988). SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275–283.PubMedCrossRefGoogle Scholar
  58. 58.
    Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E (1988). Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334:124–129.PubMedCrossRefGoogle Scholar
  59. 59.
    Dyson N, Howley PM, Munger K, Harlow E (1989). The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934–937.PubMedCrossRefGoogle Scholar
  60. 60.
    Nevins JR (1992). E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–429.PubMedCrossRefGoogle Scholar
  61. 61.
    Goodrich DW, Wang NP, Quian Y-W, Lee EY-HP, Lee W-H (1991). The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell 67:293–302.PubMedCrossRefGoogle Scholar
  62. 62.
    Gu W, Bhatia K, Magrath IT, Dong CV, Dalla-Favera R (1994). Binding and suppression of the myc transcriptional activation domain by p107. Science 264:251–254.PubMedCrossRefGoogle Scholar
  63. 63.
    Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS, Johnson BE, Skolnick MH (1994). A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440.PubMedCrossRefGoogle Scholar
  64. 64.
    Gutterman JU (1994). Cytokine therapeutics: lessons from interferon α. Proc Natl Acad Sci USA 91:1198–1205.PubMedCrossRefGoogle Scholar
  65. 65.
    Resnitzky D, Tiefenbrun N, Berissi H, Kimchi A (1992). Interferons and interleukin 6 suppress phosphorylation of the retinoblastoma protein in growth-sensitive hematopoietic cells. Proc Natl Acad Sci USA 89:402–406.PubMedCrossRefGoogle Scholar
  66. 66.
    Lu Y, Ussery GD, Muncaster MM, Gallie BL, Blanck G (1994). Evidence for retinoblastoma protein (RB) dependent and independent IFN-γ responses; RB coordinately rescues IFN-γ induction of MHC class II gene transcription in noninducible breast carcinoma cells. Oncogene 9:1015–1019.PubMedGoogle Scholar
  67. 67.
    Hatzfeld J, Li M-L, Brown EL, Sookdeo H, Levesque J-P, O’Toole T, Gurney C, Clark SC, Hatzfeld A (1991). Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor β1 or Rb oligoucleotides. J Exp Med 174:925929.Google Scholar
  68. 68.
    Lee EY-HP, Chang C-Y, Hu N, Wang Y-CJ, Lai C-C, Herrup K, Lee W-H, Bradley A (1992). Mice deficient for Rb are nonviable and show defects in neurogenesis and hematopoiesis. Nature 359:288–294.PubMedCrossRefGoogle Scholar
  69. 69.
    Jacks T, Fazei A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992). Effects of an Rb mutation in the mouse. Nature 359:295–330.PubMedCrossRefGoogle Scholar
  70. 70.
    Symonds H, Krall L, Remington L, Saenz-Robles M, Lowe S, Jacks T, Van Dyke T (1994). p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78:703–711.PubMedCrossRefGoogle Scholar
  71. 71.
    Wen S-F, Nodelman M, Nared-Hood K, Duncan J, Geradts J, Shepard HM (1994). Retinoblastoma protein monoclonal antibodies with novel characteristics. J Immunol Methods 169:231–240.PubMedCrossRefGoogle Scholar
  72. 72.
    Cheng J, Scully P, Shew J-Y, Lee W-H, Vila V, Haas M (1990). Homozygous deletion of the retinoblastoma gene in an acute lymphoblastic leukemia (T) cell line. Blood 75:730–735.PubMedGoogle Scholar
  73. 73.
    Mittnacht S, Hinds PW, Dowdy SF, Weinberg RA (1991). Modulation of retinoblastoma protein activity during the cell cycle. Cold Spring Harbor Symp Quant Biol 56:197–209.PubMedGoogle Scholar
  74. 74.
    Kornblau SM, Xu H-J, Zhang W, Xu S-X, Beran M, Smith TL, Hester J, Estey E, Benedict WF, Deisseroth AB (1994). Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia. Blood 84:256–261.PubMedGoogle Scholar
  75. 75.
    Pagliaro LC, Antelman D, Johnson DE, Machemer T, McCulloch EA, Freireich EJ, Stass SA, Shepard HM, Maneval D, Gutterman JU (1995). Recombinant human retinoblastoma protein inhibits cancer cell growth. Cell Growth Diff 6:673–680.PubMedGoogle Scholar
  76. 76.
    Kornblau SM, Xu H-J, Benedict W, Deisseroth AB (1993). Changes in retinoblastoma protein expression between diagnosis and relapse in acute myelogenous leukemia. Blood 82 (Suppl 1):111a (abstract).Google Scholar
  77. 77.
    Towatari M, Adachi K, Kato H, Saito H (1991). Absence of the human retinoblastoma gene product in the megakaryoblastic crisis of chronic myelogenous leukemia. Blood 78:2178–2181.PubMedGoogle Scholar
  78. 78.
    Furukawa Y, DeCaprio J, Belvin M, Griffin JD (1991). Heterogenous expression of the product of the retinoblastoma susceptibility gene in primary human leukemia cells. Oncogene 6:1343–1346.PubMedGoogle Scholar
  79. 79.
    Kornblau SM, Chen N, del Giglio A, O’Brien S, Deisseroth AB (1994). Retinoblastoma protein expression is frequently altered in chronic lymphocytic leukemia. Cancer Res 54:242–246.PubMedGoogle Scholar
  80. 80.
    Huang H-JS, Yee J-K, Shew J-Y, Chen P-L, Bookstein R, Friedmann T, Lee EY-HP, Lee W-H (1988). Suppression of the neoplastic phenotype by replacement of the retinoblastoma gene product in human cancer cells. Science 242:1563–1566.PubMedCrossRefGoogle Scholar
  81. 81.
    Bookstein R, Shew J-Y, Chen P-L, Scully P, Lee W-H (1990). Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247:712–715.PubMedCrossRefGoogle Scholar
  82. 82.
    Takahashi R, Hashimoto T, Xu HJ, Hu SX, Matsui T, Miki T, Bigo-Marshall H, Aaronson SA, Benedict WF (1991). The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells. Proc Natl Acad Sci USA 88:5257–5261.PubMedCrossRefGoogle Scholar
  83. 83.
    Kratzke RA, Shimizu E, Geradts J, Gerster JL, Segal S, Otterson GA, Kaye FJ (1993). RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extrtacellular matrix. Cell Growth Differ 4:629–635.PubMedGoogle Scholar
  84. 84.
    Bignon Y-J, Chen Y, Chang C-Y, Riley DJ, Windle JJ, Mellon PL, Lee W-H (1993). Expression of a retinoblastoma transgene results in dwarf mice. Genes Dev 7:1654–1662.PubMedCrossRefGoogle Scholar
  85. 85.
    Maier JA, Statuto M, Ragnotti G (1994). Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells. Mol Cell Biol 14:1845–1851.PubMedGoogle Scholar
  86. 86.
    Roghani M, Moscatelli D (1992). Basic fibroblast growth factor is internalized through both receptor-mediated and heperan sulfate-mediated mechanisms. J Biol Chem 267:22156–22162.PubMedGoogle Scholar
  87. 87.
    Vogel BE, Lee S-J, Hildebrand A, Craig W, Pierschbacher MD, Wong-Staal F, Ruoslahti E (1993). A novel integrin specificity exemplified by binding of the alpha v beta 5 integrin to the basic domain of the HIV tat protein and vitronectin. J Cell Biol 121:461–468.PubMedCrossRefGoogle Scholar
  88. 88.
    Harada S, Loten EG, Smith RM, Jarett L (1992). Nonreceptor mediated nuclear accumulation of insulin in H35 rat hepatoma cells. J Cell Physiol 153:607–613.PubMedCrossRefGoogle Scholar
  89. 89.
    Joliot AH, Triller A, Volovitch M, Pernelle C, Prochiantz A (1991). α-2,8-polysialic acid is the neuronal surface receptor of antennapedia homeobox peptide. New Biologist 11:1121–1134.Google Scholar
  90. 90.
    Burwen SJ, Jones AL (1987). The association of polypeptide hormones and growth factors with the nuclei of target cells. Trends Biochem Sci 12:159–162.CrossRefGoogle Scholar
  91. 91.
    Fujiwara T, Cai DW, Georges RN, Mukhopadhyay T, Grimm EA, Roth JA (1994). Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model. J Natl Cancer Inst 86:1458–1462.PubMedCrossRefGoogle Scholar
  92. 92.
    Liu TJ, Zhang WW, Taylor DL, Roth JA, Goepfert H, Clayman GL (1994). Growth suppression of human head and neck cancer cells by the introduction of a wild-type p53 gene via a recombinant adenovirus. Cancer Res 54:3662–3667.PubMedGoogle Scholar

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© Kluwer Academic Publishers, Boston 1996

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  • Lance C. Pagliaro

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