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Wild-Type versus Mutant p53

  • Chapter
p53 Suppressor Gene

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

What is now known as p53 was initially identified as a normal cellular protein bound to SV40 large T antigen.1,2 Immunoprecipitation of large T antigen from a transformed mouse cell line coprecipitated a nuclear phosphoprotein of 53,000 molecular weight, hence called p53. The human p53 protein is composed of 393 amino acids and is located in the nucleus. p53 is present in all tissues but in such low quantities3–5 that it is difficult to detect by immunohistochemical techniques. On the other hand, the p53 protein has been detected at much higher levels in a large number of sporadic tumors and virally and chemically-transformed cell lines from mice and humans.6,7 Isolation and characterization of the p53 gene followed by early transfection studies indicated that p53 is capable of immortalizing primary rat embryonic fibroblast cells in culture. It was also found that p53 could cooperate with activated ras oncogene in cellular transformation of primary cells in culture.8–10

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References

  1. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40transformed cells. Nature 1979; 278: 261–263.

    PubMed  CAS  Google Scholar 

  2. Linzer DIH, Levine AJ. Charactertization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 1979; 17: 43–52.

    PubMed  CAS  Google Scholar 

  3. Oren M. The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochim Biophys Acta 1985; 832: 67.

    Google Scholar 

  4. Matlashewski G, Banks L, Pim D, Crawford L. Analysis of human p53 proteins and mRNA levels in normal and transformed cells. Eur J Biochem 1986; 154: 655.

    Google Scholar 

  5. Rotter V. p53, a transformation-related cellular-encoded protein, can be used as a biochemical marker for the detection of primary mouse tumor cells. Proc Natl Acad Sci USA 1983; 80: 2613–2617.

    PubMed  CAS  Google Scholar 

  6. Deleo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci USA 1979; 76: 2420–2424.

    PubMed  CAS  Google Scholar 

  7. Appella E, Hearing VJ. p53, a transformation related protein found in chemically induced sarcomas and other transformed cells. In: Anonymous Advances in Virol Oncology. New York: Raven Press, 1982: 137.

    Google Scholar 

  8. Eliyahu D, Raz A, Gruss P, Givol D, Oren M. Participation of p53 cellular tumor antigen in transformation of normal embryonic cells. Nature 1984; 312: 646–649.

    PubMed  CAS  Google Scholar 

  9. Jenkins JR, Rudge K, Currie GA. Cellular immortalization by a cDNA clone encoding the transformation associated phosphoprotein p53. Nature 1984; 312: 651–654.

    PubMed  CAS  Google Scholar 

  10. Parada LF, Land H, Weinberg A, Wolf D, Rotter V. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 1984; 312: 649–651.

    PubMed  CAS  Google Scholar 

  11. Hinds P, Finlay C, Levine AJ. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol 1989; 63 (2): 739–746.

    PubMed  CAS  Google Scholar 

  12. Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M. Wildtype p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci USA 1989; 86: 8763–8767.

    PubMed  CAS  Google Scholar 

  13. Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell 1989; 57: 1083–1093.

    PubMed  CAS  Google Scholar 

  14. Shaulsky G, Goldfinger N, Tosky MS, Levine AJ, Rotter V. Nuclear localization is essential for the activity of p53 protein. Oncogene 1991; 6: 2055–2065.

    PubMed  CAS  Google Scholar 

  15. Meek D, Eckhart W. Phosphorylation of p53 in normal and simian virus 40 transformed NIH 3T3 cells. Mol Cell Biol 1988; 8: 461–465.

    PubMed  CAS  Google Scholar 

  16. Lees-Miller SP, Chen YR, Anderson CW. Human cells contain a DNA-activated protein kinase that phosophorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen. Mol Cell Biol 1990; 10: 6472–6481.

    PubMed  CAS  Google Scholar 

  17. Addison C, Jenkins JR, Sturzbecher HW. The p53 nuclear localization signal is structurally linked to a p34cdc2 kinase motif. Oncogene 1990; 5: 423–426.

    PubMed  CAS  Google Scholar 

  18. Biscoff JR, Friedman PN, Marshak DR, Prives C, Beach D. Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci USA 1990; 87: 4766–4770.

    Google Scholar 

  19. Sturzbecher HW, Maimets T, Chumakov P, et al. p53 interacts with p34 cdc2 in mammalian cells: implications for cell cycle control and oncogenesis. Oncogene 1990; 5: 795–802.

    PubMed  CAS  Google Scholar 

  20. Riabowol K, Draetta G, Brizuela L, Vandre D, Beach D. The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells. Cell 1989; 57: 393–401.

    PubMed  CAS  Google Scholar 

  21. Reich NC, Levine A. Growth regulation of a cellular tumor antigen, p53, in nontransformed cells. Nature 1984; 308: 199–201.

    PubMed  CAS  Google Scholar 

  22. Milner J, Milner S. SV40–53K antigen: a possible role for 53K in normal cells. Virology 1981; 112: 785–788.

    PubMed  CAS  Google Scholar 

  23. Wilcock D, Lane DP. Localization of p53, retinoblastoma, and host replication proteins at sites of viral replication in herpes-infected cells. Nature 1991; 349: 429–432.

    PubMed  CAS  Google Scholar 

  24. Kraiss S, Barnekow A, Montenarh M. Protein kinase activity associated with immunopurified p53 protein. Oncogene 1990; 5: 845–855.

    PubMed  CAS  Google Scholar 

  25. Soussi T, DeFromentel CC, Mechali M, Kress M. Cloning and characterization of a cDNA from Xenopus laevis coding for a protein homologous to human and murine p53. Oncogene 1987; 1: 71–78.

    PubMed  CAS  Google Scholar 

  26. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253: 49–53.

    PubMed  CAS  Google Scholar 

  27. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991; 351: 453–456.

    PubMed  CAS  Google Scholar 

  28. Pardee AB. G1 events and regulation of cell proliferation. Science 1989; 246: 603.

    PubMed  CAS  Google Scholar 

  29. Mercer WE, Nelson D, Deleo AB, Old LJ, Baserga R. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc Natl Acad Sci USA 1982; 79: 6309–6312.

    PubMed  CAS  Google Scholar 

  30. Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science 1990; 249: 1046–1049.

    PubMed  CAS  Google Scholar 

  31. Raycroft L, Wu H, Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 1990; 249: 1049–1051.

    PubMed  CAS  Google Scholar 

  32. Ginsberg D, Mechta F, Yaniv M, Oren M. Wild-type p53 can down-modulate the activity of various promoters. Proc Natl Acad Sci USA 1991; 88: 9979–9983.

    PubMed  CAS  Google Scholar 

  33. Santhanam U, Ray A, Sehgal PB. Repression of the interleukin-6 gene promoter by p53 and the retinoblastoma susceptibility gene products. Proc Natl Acad Sci USA 1991; 88: 7605–7609.

    PubMed  CAS  Google Scholar 

  34. Kern SE, Kinzler KW, Bruskin A, et al. Identification of p53 as a sequence-specific DNA-binding protein. Science 1991; 252: 1708–1711.

    PubMed  CAS  Google Scholar 

  35. Shaulsky G, Goldfinger N, Peled A, Rotter V. Involvement of wild-type p53 in pre-B-cell differentiation in vitro. Proc Natl Acad Sci USA 1991; 88: 8982–8986.

    PubMed  CAS  Google Scholar 

  36. Shaulsky G, Goldfinger N, Rotter V. Alterations in tumor development in vivo mediated by expression of wild-type or mutant p53 proteins. Cancer Res 1991; 51: 5232–5237.

    PubMed  CAS  Google Scholar 

  37. Kastan MB, Radin AI, Kuerbitz SJ, et al. Levels of p53 protein increase with maturation in human hematopoietic cells. Cancer Res 1991; 51: 4279.

    PubMed  CAS  Google Scholar 

  38. Rotter V, Abutbul H, Ben-Ze’ev A. p53 transformation-related protein accululates in the nucleus of transformed fibroblasts in association with the chromatin and is found in the cytoplasm of nontransformed fibroblasts. EMBO J 1983; 2: 1041–1047.

    PubMed  CAS  Google Scholar 

  39. Shaulsky G, Ben-Ze’ev A, Rotter V. Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene 1990; 5: 1707–1711.

    PubMed  CAS  Google Scholar 

  40. Deppert W, Haug M. Evidence for free and metabolically stable p53 protein in nuclear subfractions of simian virus 40-transformed cells. Mol Cell Biol 1986; 6: 2233–2240.

    PubMed  CAS  Google Scholar 

  41. Shaulsky G, Goldfinger N, Ben-Ze’ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol 1990; 10: 6567–6577.

    Google Scholar 

  42. Milner J, Cook A. Visualization, by immunocytochemistry, of p53 at the plasma membrane of both nontransformed and SV40-transformed cells. Virology 1986; 150: 265–269.

    PubMed  CAS  Google Scholar 

  43. Levine AJ. The tumor suppressor genes. Ann Rev Biochem 1993; 62: 623–651.

    PubMed  CAS  Google Scholar 

  44. Marshall CJ. Tumor suppressor genes. Cell 1991; 64: 313–326.

    PubMed  CAS  Google Scholar 

  45. Gannon JV, Lane DP. p53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature 1987; 329: 456–458.

    PubMed  CAS  Google Scholar 

  46. Braithwaite AW, Sturzbevcher HW, Addison C, Palmer C, Rudge K, Jenkins JR. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature 1987; 329: 458–460.

    PubMed  CAS  Google Scholar 

  47. Chen P-L, Chen Y, Bookstein R, Lee W-H. Genetic mechanisms of tumor suppression by the human p53 gene. Science 1990; 250: 1576–1580.

    PubMed  CAS  Google Scholar 

  48. Mercer WE, Shields MT, Amin M, et al. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 1990; 87: 6166–6170.

    PubMed  CAS  Google Scholar 

  49. Diller L, Kassel J, Nelson CE, et al. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 1990;(11):5772–5781.

    Google Scholar 

  50. Baker SJ, Markowitz S, Fearson ER, Villson JKV, Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 1990; 249: 912–915.

    PubMed  CAS  Google Scholar 

  51. Wyllie FS, Dawson T, Bond JA, et al. Correlated abnormalities of transforming growth factor beta 1 response and p53 expression in thyroid epithelial cell transformation. Mol Cell Endocrinology 1991; 76: 13–21.

    CAS  Google Scholar 

  52. Benchimol S, Pim D, Crawford L. Radioimmunoassay of the cellular protein p53 in mouse and human cell lines. EMBO J 1982; 1: 1055–1062.

    PubMed  CAS  Google Scholar 

  53. Coffman RL, Weissman IL. A monoclonal antibody which recognizes B cell and B cell precursors in mice. J Exp Med 1981; 153: 269–279.

    PubMed  CAS  Google Scholar 

  54. Dippold WG, Jay G, DeLeo A, Khoury G, Old LJ. p53 transformation related protein: detection by monoclonal antibody in mouse and human cells. Natl Acad Sci USA 1981; 78: 1695–1699.

    CAS  Google Scholar 

  55. Gurney EG, Harrison RO, Fenno J. Moloclonal antibodies against simian virus 40 T antigens: evidence for distinct subclasses of large T antigen and for similarities among nonviral T antigens. J Virol 1980; 34: 752–763.

    PubMed  CAS  Google Scholar 

  56. Harlow E, Crawford LV, Pim DC, Williamson NM. Monoclonal antibodies specific for the SV40 tumor antigens. J Virol 1981; 39: 861–869.

    PubMed  CAS  Google Scholar 

  57. Rotter V, Friedman H, Katz A, Zerivitz K, Wolf D. Variation in antigenic determinants of p53 transformation-related protein obtained from various species. J Immunol 1983; 131: 329–333.

    PubMed  CAS  Google Scholar 

  58. Yewell J, Gannon JV, Lane DP. Monoclonal antibody analysis of p53 expression in normal and transformed cells. J Virol 1986; 59: 444–452.

    Google Scholar 

  59. Thomas R, Kaplan L, Reich N, Lane DP, Levine AJ. Characterization of human p53 antigens employing primate specific monoclonal antibodies. Virology 1983; 131: 502–517.

    PubMed  CAS  Google Scholar 

  60. Gannon JV, Greaves R, Iggo R, Lane DP. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 1990; 9: 1595–1602.

    PubMed  CAS  Google Scholar 

  61. Milner JA, Cook A, Sheldon M. A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40. Oncogene 1987; 1: 453–455.

    PubMed  CAS  Google Scholar 

  62. Steinmeyer K, Maacke H, Deppert W. Cell cycle control by p53 in normal (3T3) and chemically transformed (Meth A) mouse cells. I. regulation of p53 expression. Oncogene 1990; 5: 1691–1699.

    PubMed  CAS  Google Scholar 

  63. Deppert W, Haug M, Steinmayer T. Modulation of p53 protein expreslion during cellular transformation with simian virus 40. Mol Cell Biol 1987; 7: 4453–4463.

    PubMed  CAS  Google Scholar 

  64. Shohat O, Greenberg M, Reisman D, Oren M, Rotter V. Inhibition of cell growth mediated by plasmids encoding p53 anti-sense. Oncogene 1987; 1: 277–283.

    PubMed  CAS  Google Scholar 

  65. Milner J, Watson JV. Addition of fresh medium induces cell cycle and conformation changes in p53, a tumour suppressor protein. Oncogene 1990; 5: 1683–1690.

    PubMed  CAS  Google Scholar 

  66. Mora PT, Chandrasekaran K, Hoffman JC, MacFarland VW. An embryo protein induced by SV40 virus transformation of mouse cells. Nature 1980; 288: 722–724.

    PubMed  CAS  Google Scholar 

  67. Segal S, Levine AJ, Khoury G. Evidence for nonspliced SV40 RNA in undifferentiated murine teratocarcinoma stem cells. Nature 1979; 280: 335–338.

    PubMed  CAS  Google Scholar 

  68. Rogel A, Popliker M, Webb CG, Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol 1985; 5: 2851–2855.

    PubMed  CAS  Google Scholar 

  69. Louis JM, McFarland VW, May P, Mora PT. The phosphoprotein p53 is down-regulated post-transcriptionally during embryogenesis in vertebrates. Biochim Biophys Acta 1988; 950: 395–402.

    PubMed  CAS  Google Scholar 

  70. Dony C, Kessel M, Gruss P. Post-transcriptional control of c-myc and p53 expression during differentiation of the embryonal carcinoma cell line F9. Nature 1985; 317: 636–639.

    PubMed  CAS  Google Scholar 

  71. Schmid P, Lorenz A, Hameister H, Montenarh M. Expression of p53 during mouse embryogenesis. Development 1991; 113: 857–865.

    PubMed  CAS  Google Scholar 

  72. Bendori R, Resnitsky D, Kimchi A. Changes in p53 mRNA expression during terminal differentiation of murine erythroleukemia cells. FEBS Lett 1983; 162: 384–389.

    CAS  Google Scholar 

  73. Bendori R, Restinzky D, Kimchi A. Changes in p53 mRNA expression during terminal differentiation of murine erythroleukemia cells. Virology 1987; 161: 607–611.

    PubMed  CAS  Google Scholar 

  74. Khochbin S, Principaud E, Chabanas A, Lawrence JJ. Early events in murine erythroleukemia cells induced to differentiate. J Mol Biol 1988; 200: 55–64.

    PubMed  CAS  Google Scholar 

  75. Klinken SP, Holmes KL, Morse HCI, Thorgeirsson SS. Transcriptional and post-transcriptional regulation of c-myc, c-myb, and p53 during proliferation and differentiation of murine erythroleukemia cells treated with DFMO and DMSO. Exp Cell Res 1988; 178: 185–198.

    PubMed  CAS  Google Scholar 

  76. Richnon VM, Ramsay RG, Rifkind RA, Marks PA. Modulation of the c-myb, c-myc and p53 mRNA and protein levels during induced murine erythroleukemia cell differentiation. Oncogene 1989; 4: 165–173.

    Google Scholar 

  77. Shen D-W, Real FX, Deleo AB, Old LJ, Marks PA, Rifkind RA. Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division. Proc Natl Acad Sci USA 1983; 80: 5919–5922.

    PubMed  CAS  Google Scholar 

  78. Khochbin S, Lawrence JJ. An antisense RNA involved in p53 mRNA maturation in murine erythroleukemia cells induced to differentiate. EMBO J 1989; 8: 4107–4114.

    PubMed  CAS  Google Scholar 

  79. Khochbin S, Lawrence JJ. Processing of p53 mRNA during induced differentiation of murine erythroleukemia cells: is an altered splicing mechanism responsible for the post-transcriptional control of gene expression? Gene 1988; 72: 177–181.

    Google Scholar 

  80. Chandrasekaran K, Mora PT, Nagarajan L, Anderson WB. The amount of a specific cellular protein (p53) is a correlate of differentiation in embryonal carcinoma cells. J Cell Physiol 1982; 113: 134–140.

    PubMed  CAS  Google Scholar 

  81. Clarke CF, Cheng K, Frey AB, Stein R, Hinds PW, Levine AJ. Purification of complexes of nuclear oncogene p53 with rat and Escherichia coli heat shock proteins: in vitro dissociation of hsc 70 and DNA K from murine p53 by ATP. Mol Cell Biol 1988; 8: 1206–1215.

    PubMed  CAS  Google Scholar 

  82. Maltzman W, Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 1984; 4: 1689–1694.

    PubMed  CAS  Google Scholar 

  83. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51: 6304–6311.

    PubMed  CAS  Google Scholar 

  84. Yonish-Rouach E, Resnitzky D, Rotem J, Sachs L, Kimchi A, Oren M. Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin-6. Nature 1991; 352: 345–347.

    PubMed  CAS  Google Scholar 

  85. Lane DP, Crawford LV. T antigen is bound to host protein in SV40transformed cells. Nature 1979; 351: 453–456.

    Google Scholar 

  86. Sarnow P, Ho YS, Williams J, Levine AJ. Adenovirus E1B-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54kd cellular protein in transformed cells. Cell 1982; 28: 387–396.

    PubMed  CAS  Google Scholar 

  87. Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus 16 E7 oncoprotein in able to bind to retinoblastoma gene product. Science 1989; 243: 936–937.

    Google Scholar 

  88. Szekely L, Selivanova S, Magnusson KP, Klein G, Wiman KG. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins. Proc Natl Acad Sci 1993; 90: 5455–5459.

    PubMed  CAS  Google Scholar 

  89. Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC. Hepatitis-B virus x-protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci USA 1994; 91: 2230–2234.

    PubMed  CAS  Google Scholar 

  90. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 Oncogene Product Forms a Complex with the p53 Protein and Inhibits p53-Mediated Transactivation. Cell 1992; 69: 1237–1245.

    PubMed  CAS  Google Scholar 

  91. Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes and Dev 1993; 7: 1126–1132.

    PubMed  CAS  Google Scholar 

  92. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumor types. Nature 1989; 342: 705–708.

    PubMed  CAS  Google Scholar 

  93. Vogelstein B. Cancer: A deadly inheritance. Nature 1990; 348: 681–682.

    CAS  Google Scholar 

  94. Soussi T, Caron de Fromentel C, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene 1990; 5: 945–952.

    PubMed  CAS  Google Scholar 

  95. Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ. Activating mutations for transformation by p53 produce a gene product that forms an hsc 70-p53 complex with an altered half-life. Mol Cell Biol 1988; 8: 531–539.

    PubMed  CAS  Google Scholar 

  96. Hinds PW, Finlay CA, Quartin RS, et al. Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the “hot spot” mutant phenotypes. Cell Growth and Differentation 1990; 1: 571–580.

    CAS  Google Scholar 

  97. Rodrigues NR, Rowan A, Smith MEF, et al. p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 1990; 87: 7555–7559.

    PubMed  CAS  Google Scholar 

  98. Baker SJ, Preisinger AC, Jessup JM, et al. p53 gene mutations occur in combination wiht 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 1990; 50: 7717–7722.

    PubMed  CAS  Google Scholar 

  99. Shaw P, Tardy S, Benito E, Obrador A, Costa J. Occurrence of Ki-ras and p53 mutations in primary colorectal tumors. Oncogene 1991; 6: 2121.

    Google Scholar 

  100. Ishioka C, Sato T, Gamoh M, et al. Mutations of the p53 gene, including an intronic point mutation, in colorectal tumors. Biochem Biophys Res Commun 1991; 177: 901.

    PubMed  CAS  Google Scholar 

  101. Takahashi T, Suzuki H, Hida T, Sekido Y, Ariyoshi Y, Ueda R. The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. Oncogene Research 1991; 6: 1755–1778.

    Google Scholar 

  102. Hensel CH, Xiang RH, Sakaguchi AY, Naylor SL. Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. Oncogene 1991; 6: 1067–1071.

    PubMed  CAS  Google Scholar 

  103. Sidransky D, Von Eschenbach A, Tsai YC, et al. Identification of p53 gene mutations in bladder cancers and urine samples. Science 1991; 252: 706–709.

    PubMed  CAS  Google Scholar 

  104. Isaacs WB, Carter BS, Ewing CM. Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res 1991; 51: 4716–4720.

    PubMed  CAS  Google Scholar 

  105. Farrell PJ, Allan GJ, Shanahan F, Vousden KH, Crook T. p53 is frequently mutated in Burkitt’s lymphoma cell lines. EMBO J 1991; 10: 2879.

    Google Scholar 

  106. Gaidano G, Ballerini P, Gong JZ, et al. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci USA 1991; 88: 5413–5417.

    PubMed  CAS  Google Scholar 

  107. Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 1991; 350: 429–431.

    PubMed  CAS  Google Scholar 

  108. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 350: 427–428.

    PubMed  CAS  Google Scholar 

  109. Murakami Y, Hayashi K, Hirohashi S, Sekiya T. Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res 1991; 51: 5520.

    PubMed  CAS  Google Scholar 

  110. Cheng J, Haas M. Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines. Mol Cell Biol 1990; 10: 5502–5509.

    PubMed  CAS  Google Scholar 

  111. Nagai H, Kinoshita T, Imamura J, et al. Genetic alteration of p53 in some patients wiht adult T-cell leukemia. Jpn J Cancer Res 1991; 82: 1421.

    PubMed  CAS  Google Scholar 

  112. Chung R, Whaley J, Kley N, et al. TP53 gene mutations and 17p deletions in human astrocytomas. Genes Chromosomes Cancer 1991; 3: 323.

    PubMed  CAS  Google Scholar 

  113. Chiba I, Takahashi T, Nau MM, et al. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Oncogene 1990; 5: 1603–1610.

    PubMed  CAS  Google Scholar 

  114. Sugimoto K, Toyoshima H, Sakai R, et al. Mutations of the p53 gene in lymphoid leukemia. Blood 1991; 77: 1153.

    PubMed  CAS  Google Scholar 

  115. Bennett WP, Hollstein MC, He A, et al. Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene 1991; 6: 1779–1784.

    PubMed  CAS  Google Scholar 

  116. Hollstein MC, Peri L, Mandard AM, et al. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. Cancer Res 1991; 51: 4102–4106.

    PubMed  CAS  Google Scholar 

  117. Hollstein MC, Metcalf RA, Welsh JA, Montesano R, Harris CC. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci USA 1990; 87: 9958–9961.

    PubMed  CAS  Google Scholar 

  118. Matozaki T, Sakamoto C, Matsuda K, et al. Missense mutations and a deletion of the p53 gene in human gastric cancer. Biochem Biophys Res Commun 1992; 182: 215.

    PubMed  CAS  Google Scholar 

  119. Tamura G, Kihana T, Nomura K, Terada M, Sugimura T, Hirohashi S. Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res 1991; 51: 3056–3058.

    PubMed  CAS  Google Scholar 

  120. Mazars R, Pujol P, Maudelonde T, Jeanteur P, Theillet C. p53 mutations in ovarian cancer: a late event? Oncogene 1991; 6: 1685.

    PubMed  CAS  Google Scholar 

  121. Okamoto A, Sameshima Y, Yokoyama S, et al. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Caner Res 1991; 51: 5171.

    CAS  Google Scholar 

  122. Slingerland JM, Minden MD, Benchimol S. Mutation of the p53 gene in human acute myelogenous leukemia. Blood 1991; 77: 1500.

    PubMed  CAS  Google Scholar 

  123. Kovach JS, McGovern RM, Cassady JD, et al. Direct sequencing from touch preparations of human carcinomas: analysis of p53 mutations in breast carcinomas. J Natl Cancer Inst 1991; 83 (14): 1004–1009.

    PubMed  CAS  Google Scholar 

  124. Menon AG, Anderson KM, Riccardi VM, et al. Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Rechlinghausen neurofibromatosis. Proc Natl Acad Sci USA 1990; 87: 5435.

    PubMed  CAS  Google Scholar 

  125. Osborne RJ, Merlo GR, Mitsudomi T, et al. Mutations in the p53 gene in primary human breast cancers. Cancer Res 1991; 51: 6194.

    PubMed  CAS  Google Scholar 

  126. Borresen A-L, Hovig E, Malkin D, et al. Constant denaturant gel electrophoresis as a rapid screening technique for p53 mutations. Proc Natl Acad Sci USA 1991; 88: 8405–8409.

    PubMed  CAS  Google Scholar 

  127. Runnebaumn IB, Nagarajan M, Bowman M, Soto D, Sukumar S. Mutations in p53 as potential molecular markers for human breast cancer. Proc Natl Acad Sci USA 1991; 88: 10657.

    Google Scholar 

  128. Chen L-C, Neubauer A, Kurisu W, et al. Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer. Proc Natl Acad Sci USA 1991; 88: 3847–3851.

    PubMed  CAS  Google Scholar 

  129. Prosser J, Thompson AM, Cranston G, Evans HJ. Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. Oncogene 1990; 5: 1573–1580.

    PubMed  CAS  Google Scholar 

  130. Stratton MR, Moss S, Warren W, et al. Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene. Oncogene 1990; 5: 1297–1301.

    PubMed  CAS  Google Scholar 

  131. Okamoto A, Sameshima Y, Yamada Y, et al. Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. Cancer Res 1991; 51: 5632.

    PubMed  CAS  Google Scholar 

  132. Ohgaki H, Eibl RH, Wiestler OD, Yasargil MG, Newcomb EW, Kleinhues P. p53 mutations in nonastrocytic human brain tumors. Cancer Res 1991; 51: 6202.

    PubMed  CAS  Google Scholar 

  133. Mashiyama S, Murakami Y, Yoshimoto T, Sekiya T, Hayashi K. Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene 1991; 6: 1313–1318.

    PubMed  CAS  Google Scholar 

  134. Shirasawa S, Urabe K, Yanagawa Y, Toshitani K, Iwama T, Sasazuki T. p53 gene mutations in colorectal tumors from patients with familial polyposis coli. Cancer Rec 1991; 51: 2874.

    Google Scholar 

  135. Sturzbecher H-W, Chumakow P, Welch WJ, Jenkins JR. Mutant p53 proteins bind hsp 72/73 cellular heat shock-related proteins in SV40 transformed monkey cells. Oncogene 1987; 1: 201–211.

    PubMed  CAS  Google Scholar 

  136. Gannon JV, Greaves R, Iggo R, Lane DP. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 1990; 9: 1595–1602.

    PubMed  CAS  Google Scholar 

  137. Reihsaus E, Kohler. M, Kraiss S, Oren M, Montenarh M. Regulation of the level of the oncoprotein p53 in non-transformed and transformed cells. Oncogene 1990; 5: 137–145.

    PubMed  CAS  Google Scholar 

  138. Kraiss S, Spiess S, Reihsaus E, Montenarh M. Correlation of metabolic stability and altered quaternary structure of oncoprotein p53 with cell transformation. Exp Cell Res 1991; 192: 157–164.

    PubMed  CAS  Google Scholar 

  139. Milner J, Medcalf EA. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 1991; 65: 765–774.

    PubMed  CAS  Google Scholar 

  140. Michalovitz D, Halevy O, Oren M. Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell 1990; 62: 671–680.

    PubMed  CAS  Google Scholar 

  141. Ginsberg D, Michael-Michalovitz D, Oren M. Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein. Mol Cell Biol 1991; 11: 582–585.

    PubMed  CAS  Google Scholar 

  142. Halevy O, Michalovitz D, Oren M. Different tumor-derived p53 mutants exhibit distinct biological activities. Science 1990; 250: 113–116.

    PubMed  CAS  Google Scholar 

  143. Gronostajski RM, Goldberg AL, Pardee AB. Energy requirement for degradation of tumor-associated protein 53. Mol Cell Biol 1984; 4: 442–448.

    PubMed  CAS  Google Scholar 

  144. Ciechanover A, DiGiuseppe JA, Bercovich B, et al. Degradatin of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci USA 1991; 88: 139–143.

    PubMed  CAS  Google Scholar 

  145. Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc Natl Acad Sci 1992; 89: 7262–7266.

    PubMed  CAS  Google Scholar 

  146. Harvey DM, Levine AJ. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes and Development 1991; 5: 2375–2385.

    PubMed  CAS  Google Scholar 

  147. Rovinski B, Benchimol S. Immortalization of rat embryo fibroblasts by the cellular p53 oncogene. Oncogene 1988; 2: 445–452.

    PubMed  CAS  Google Scholar 

  148. Mercer WE, Shields MT, Amin M, et al. Antiproliferative effects of wild-type human p53. J Cell Biochem 1990; 14C: 285.

    Google Scholar 

  149. Martinez J, Georgoff I, Levine AJ. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes and Development 1991; 5: 151–159.

    PubMed  CAS  Google Scholar 

  150. Wolf D, Harris N, Rotter V. Reconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene. Cell 1984; 38: 119–126.

    PubMed  CAS  Google Scholar 

  151. Corominas M, Kamino H, Leon J, Pellicer A. Oncogene activation in human benign tumors of the skin (keratoacanthomas): is HRAS involved in differentiation as well as proliferation? Proc Natl Acad Sci USA 1989; 86: 6372–6376.

    PubMed  CAS  Google Scholar 

  152. Sturzbecher HW, Bain R, Addisoin C, et al. A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene 1992; 7: 1513–1523.

    PubMed  CAS  Google Scholar 

  153. Vogelstein B, Fearon ER, Kern SE, et al. Allelotype of colorectal carcinomas. Science 1989; 244: 207–211.

    PubMed  CAS  Google Scholar 

  154. Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989; 244: 217–221.

    PubMed  CAS  Google Scholar 

  155. Coles C, Thompson AM, Elder PA, et al. Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. Lancet 1990; 336: 76–78.

    Google Scholar 

  156. Cornelis RS, van Veliet M, Vos CBJ, et al. Evidence for a gene on 17p13.3, distal to TP53, as a target for allele loss in breats tumors without p53 mutations. Cancer Res 1994; 54: 4200–4206.

    PubMed  CAS  Google Scholar 

  157. Thompson AM, Steel CM, Chetty U, et al. p53 gene mRNA expression and chromosome 17p allele loss in breast cancer. Br J Cancer 1990; 61: 74–78.

    PubMed  CAS  Google Scholar 

  158. Sato T, Tanigami A, Yamakawa K, et al. Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res 1990; 50: 7184–7189.

    PubMed  CAS  Google Scholar 

  159. Li FP. Cancer Families: Human models of susceptibility to neoplasia from the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 1988; 48: 5381–5386.

    PubMed  CAS  Google Scholar 

  160. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250: 1233–1238.

    PubMed  CAS  Google Scholar 

  161. Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 1990; 348: 747–749.

    PubMed  CAS  Google Scholar 

  162. Wild CP, Jiang YZ, Allen SJ, Jansen LAM, Hall AJ, Montesano R. Aflotoxin-albumin adducts in human sera from different regions of the world. Carcinogenesis 1990; 11: 2271–2274.

    PubMed  CAS  Google Scholar 

  163. Mori N, Yokota J, Oshimura M, et al. Concordant deletions of chromosome 3p and loss of heterozygosity for chromosomes 13 and 17 in small cell lung carcinoma. Cancer Res 1989; 49: 5130.

    PubMed  CAS  Google Scholar 

  164. Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T. Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci USA 1987; 84: 9252–9256.

    PubMed  CAS  Google Scholar 

  165. Yano T, Linehan M, Anglard P, et al. Genetic changes in human adenocortical carcinomas. J Natl Cancer Inst 1989; 81: 518.

    PubMed  CAS  Google Scholar 

  166. Blount PL, Ramel S, Raskind WH, et al. 17 allelic deletions and p53 protein overexpression in Barrett’s adenocarcinoma. Cancer Res 1991; 51: 5482–5486.

    PubMed  CAS  Google Scholar 

  167. Weston A, Willey JC, Modali R, et al. Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the lung. Proc Natl Acad Sci USA 1989; 86: 5099–5103.

    CAS  Google Scholar 

  168. Sano T, Tsujino T, Yoshida K, et al. Frequent loss of heterozygosity on chromosomes lq, 5q, and 17p in human gastric carcinomas. Cancer Res 1991; 51: 2926.

    Google Scholar 

  169. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319: 525–532.

    PubMed  CAS  Google Scholar 

  170. Delattre O, Olschwang S, Law DJ, et al. Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 1989; 8659: 353.

    Google Scholar 

  171. Toguchida J, Ishizaki K, Nakamura Y, et al. Assignment of common allele loss in osteosarcoma to the subregion 17p131. Cancer Res 1989; 49: 6247.

    PubMed  CAS  Google Scholar 

  172. Mulligan LM, Matlashewski GJ, Scrable HJ, Cavenee WK. Mechanisms of p53 loss in human sarcomas. Proc Natl Acad Sci USA 1990; 87: 5863–5867.

    PubMed  CAS  Google Scholar 

  173. Varley JM, Brammar. WJ, Lane DP, Swallow JE, Dolan C, Walker RA. Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinoma. Oncogene 1991; 6: 413.

    PubMed  CAS  Google Scholar 

  174. Mackay J, Steel CM, Elder PA, Forrest AP, Evans HJ. Allele loss on short arm of chromosome 17 in breast cancers. The Lancet 1988; 11: 1384–1385.

    Google Scholar 

  175. Devilee P, van Vliet M, van Sloun P, et al. Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q. Oncogene 1991; 6: 1705.

    PubMed  CAS  Google Scholar 

  176. Eccles DM, Cranston G, Steel CM, Nakamura Y, Leonard RCF. Allele losses on chromosome 17 in human epithelial ovarian carcinoma. Oncogene 1990; 5: 1599.

    PubMed  CAS  Google Scholar 

  177. Lee JH, Kavanagh JJ, Wildrick DM, Wharton JT, Blick M. Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res 1990; 50: 2724.

    Google Scholar 

  178. Sato T, Saito H, Morita R, Koi S, Lee JH, Nakamura Y. Allelotype of human ovarian cancer. Cancer Res 1991; 51: 5118.

    PubMed  CAS  Google Scholar 

  179. Russel SEH, Hickey GI, Lowry WS, White P, Atkinson RJ. Allele loss from chromosome 17 in ovarian cancer. Oncogene 1990; 5: 1581.

    Google Scholar 

  180. Olumi AF, Tsai YC, Nichols PW, et al. Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder. Cancer Res 1990; 50: 7081.

    PubMed  CAS  Google Scholar 

  181. Oka K, Ishikawa J, Bruner JM, Takahashi R, Saya H. Detection of loss of heterozygosity in the p53 gene in renal cell carcinoma and bladder cancer using the polymerase chain reaction. Mol Carcinogenesis 1991; 4: 10.

    CAS  Google Scholar 

  182. Slagle BL, Zhou YA, Butel JS. Hepatitis B virus integration even in human chromosome 17p near the p53 gene identifies the region of the chromosome commonly deleted in virus-positive hepatocellular carcinomas. Cancer Res 1991; 51: 49.

    PubMed  CAS  Google Scholar 

  183. Fujimori M, Tokino T, Hino O, et al. Allelotype study of primary hepatocellular carcinoma. Cancer Res 1991; 51: 89.

    PubMed  CAS  Google Scholar 

  184. Wagata T, Ishizaki K, Imamura M, Shimada Y, Ikenaga M, Tobe T. Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer Res 1991; 51: 2113–2117.

    PubMed  CAS  Google Scholar 

  185. Meltzer SJ, Yin J, Huang Y, et al. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc Natl Acad Sci USA 1991; 88: 4976–4980.

    PubMed  CAS  Google Scholar 

  186. Tsai YC, Nichols PW, Hiti AL, Williams Z, Skinner DG, Jones PA. Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer. Cancer Res 1990; 50: 44.

    CAS  Google Scholar 

  187. Bergerheim U, Nordenskjold M, Collins VP. Deletion mapping in human renal cell carcinoma. Cancer Res 1989; 49: 1390.

    PubMed  CAS  Google Scholar 

  188. Cogen PH, Daneshvar L, Metzger AK, Edwards MSB. Deletion mapping of the medulloblastoma locus on chromosome 17p. Genomics 1990; 8: 279.

    PubMed  CAS  Google Scholar 

  189. James CD, Carlbom E, Nordenskjold M, Collins VP, Cavenee WK. Mitotic recombination of chromosome 17 in astrocytomas. Proc Natl Acad Sci USA 1989; 86: 2858–2862.

    PubMed  CAS  Google Scholar 

  190. El-Azouzi M, Chung RY, Farmer GE, et al. Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci USA 1989; 86: 7186.

    PubMed  CAS  Google Scholar 

  191. Fults D, Tippets RH, Thomas GA, Nakamura Y, White R. Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma. Cancer Res 1989; 49: 6572.

    PubMed  CAS  Google Scholar 

  192. Cabinaillas F, Pathak S, Trujillo J, et al. Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma. Cancer Res 1988; 48: 5557.

    Google Scholar 

  193. Mashal R, Shtalrid M, Talpaz M, et al. Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. Blood 1990; 75: 180.

    PubMed  CAS  Google Scholar 

  194. Dracopoli NC, Houghton AN, Old LJ. Loss of polymorphic restriction fragments in malignant melanoma: implications for tumor heterogeneity. Proc Natl Acad Sci USA 1985; 82: 1470.

    PubMed  CAS  Google Scholar 

  195. Lavigueru A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol 1989; 9: 3982–3991.

    Google Scholar 

  196. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356: 215–221.

    PubMed  CAS  Google Scholar 

  197. Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of B-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985; 230: 1350–1354.

    PubMed  CAS  Google Scholar 

  198. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989; 86: 2766–2770.

    PubMed  CAS  Google Scholar 

  199. Lehman TA, Bennett WP, Metcalf RA, et al. p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res 1991; 51: 4090–4096.

    PubMed  CAS  Google Scholar 

  200. Herskowitz I. Functional inactivation of genes by dominant negative mutations. Nature 1987; 329: 219–222.

    PubMed  CAS  Google Scholar 

  201. Ehrhart JC, Duthu A, Ullrich S, Appella E, May P. Specific interaction between a subset of the p53 protein family and heat shock proteins hsp72/ hsc73 in a human osteosarcoma cell line. Oncogene 1988; 3: 595–603.

    PubMed  CAS  Google Scholar 

  202. Milner J, Medcalf EA, Cook AC. Tumor suppressor p53: analysis of wild-type and mutant p53 complexes. Mol Cell Biol 1991; 11: 12–19.

    PubMed  CAS  Google Scholar 

  203. Kraiss S, Quaiser A, Oren M, Montenarh M. Oligomerization of oncoprotein p53. J Virol 1988; 62: 4737–4744.

    PubMed  CAS  Google Scholar 

  204. Hinds PW, Finlay CA, Frey AB, Levine AJ. Immunological evidence for the association of p53 with a heat shock protein, hsc 709, in p53-plusras-transformed cell lines. Mol Cell Biol 1987; 7: 2863–2869.

    PubMed  CAS  Google Scholar 

  205. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250: 1233–1238.

    PubMed  CAS  Google Scholar 

  206. Srivasta S, Zou Z, Pirollo K, Blattner W, Chang ES. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 1990; 348: 747–749.

    Google Scholar 

  207. Casey G, Lo-Hsueh M, Lopez ME, Vogelstein B, Stanbridge EJ. Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene. Oncogene 1991; 6: 1791–1797.

    PubMed  CAS  Google Scholar 

  208. Chen PL, Chen Y, Bookstein R, Lee WH. Genetic mechanisms of tumor suppression by the human p53 gene. Science 1990; 250: 1576–1580.

    PubMed  CAS  Google Scholar 

  209. Takahashi T, Carbone D, Nau MM, et al. Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res 1992; 52: 2340–2343.

    PubMed  CAS  Google Scholar 

  210. Takahashi T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989; 246: 491–494.

    PubMed  CAS  Google Scholar 

  211. Shrieve DC, Bump EA, Rice GC. J Biol Chem 1988; 263: 14107.

    PubMed  CAS  Google Scholar 

  212. Wright PA, Lemoine NR, Goretzki PE, et al. Mutation of the p53 gene in a differential human thyroid carcinoma cell line, but not in primary thyroid tumors. Oncogene 1991; 6: 1693–1697.

    PubMed  CAS  Google Scholar 

  213. Ponchel F, Puisieux A, Tabone E, et al. Hepatocarcinoma-specific mutant p53–249ser induces mitotic activity but has no effect on transforming growth factor ß1-mediated apoptosis. Cancer Res 1994; 54: 2064–2068.

    PubMed  CAS  Google Scholar 

  214. Iggo R, Gatter K, Bartek J, Lane D, Harris AL. Increased expression of mutant forms of p53 oncogene in primary lung cancer. The Lancet 1990; 335: 675–679.

    CAS  Google Scholar 

  215. Mitsudomi T, Steinberg SM, Nau MM, et al. p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 1992; 7: 171–180.

    PubMed  CAS  Google Scholar 

  216. Miller CW, Aslo A, Tsay C, et al. Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer Res 1991; 50: 7950–7954.

    Google Scholar 

  217. Casson AG, Mukhopadhyay T, Cleary KR, Ro JY, Levin B, Roth JA. p53 gene mutations in Barrett’s epithelium and esophageal cancer. Cancer Res 1991; 51: 4495–4499.

    PubMed  CAS  Google Scholar 

  218. Marks JR, Davidoff AM, Kerns BJ, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 1991; 51: 2979–2984.

    PubMed  CAS  Google Scholar 

  219. Munger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 1989; 8: 4099–4105.

    PubMed  CAS  Google Scholar 

  220. Ahuja H, Bar-Eli M, Advani SH, Benchimol S, Cline MJ. Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. Proc Natl Acad Sci USA 1989; 86: 6783–6787.

    PubMed  CAS  Google Scholar 

  221. Davidoff AM, Humphrey PA, Iglehart JD, Marks JR. Genetic basis for p53 overexpression in human breast cancer. Proc Natl Acad Sci USA 1991; 88: 5006–5010.

    PubMed  CAS  Google Scholar 

  222. McMahon G, Davis EF, Huber LJ, Kim Y, Wogan GN. Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin 01-induced rat liver tumors. Proc Natl Acad Sci USA 1990; 87: 1104–1108.

    PubMed  CAS  Google Scholar 

  223. Muench KF, Misra RP, Humayun MZ. Sequence specificity in aflatoxin B1-DNA interactions. Proc Natl Acad Sci USA 1983; 80: 6–10.

    PubMed  CAS  Google Scholar 

  224. Aguilar F, Harris CC, Sun T, Hollstein M, Cerutti P. Geographic variation of p53 mutational profile in nonmalignant human liver. Science 1994; 264: 1317–1319.

    PubMed  CAS  Google Scholar 

  225. Harris AL. Telling changes of base. Nature News and Views 1991; 350: 377–378.

    CAS  Google Scholar 

  226. Frebourg T, Kassel J, Lam KT, et al. Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. Proc Natl Acad Sci USA 1992; 89: 6413–6417.

    PubMed  CAS  Google Scholar 

  227. Crook T, Wrede D, Vousden KH. p53 point mutation in HPV-negative human cervical carcinoma cell lines. Oncogene 1991; 6: 873–875.

    PubMed  CAS  Google Scholar 

  228. Crook T, Wrede D, Tidy J, Scholefield J, Crawford L, Vousden KH. Status of c-myc, p53 and retinoblastoma genes in human papillomavirus positive and negative squamous cell carcinomas of the anus. Oncogene 1991; 6: 1251–1257.

    PubMed  CAS  Google Scholar 

  229. Brash DE, Rudolph JA, Simon JA, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 1991; 88: 10124–10128.

    PubMed  CAS  Google Scholar 

  230. Romano JW, Ehrhart JC, Duthu A, Kim CM, Appella E, May P. Identification and characterization of a p53 gene mutation in a human osteosarcoma cell line. Oncogene 1989; 4: 1483–1488.

    PubMed  CAS  Google Scholar 

  231. Davidoff AM, Kerns B-JM, Iglehart JD, Marks JR. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res 1991; 51: 2605.

    Google Scholar 

  232. Gusterson BA, Anbazhagan R, Warren W, et al. Expression of p53 in premalignant and malignant squamous epithelium. Oncogene 1991; 6: 1785–1789.

    PubMed  CAS  Google Scholar 

  233. Santibanez-Koref MF, Birch JM, Hartley AL, et al. p53 germline mutations in Li-Fraumeni syndrome. Lancet 1991; 338: 1490.

    PubMed  CAS  Google Scholar 

  234. Bartek J, Iggo R, Gannon J, Lane DP. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene 1990; 5: 893.

    PubMed  CAS  Google Scholar 

  235. Fenaux P, Jonveaux P, Quiquandon I, et al. p53 gene mutations in acute myeloid leukemia with 17p monosomy. Blood 1991; 78: 1652.

    PubMed  CAS  Google Scholar 

  236. Mukhopadhyay T, Roth JA. A codon 248 p53 mutation retains tumor suppressor function as shown by enhancement of tumor growth by antisense p53. Can Res 1993; 53: 4362–4366.

    CAS  Google Scholar 

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    Tapas Mukhopadhyay Ph.D., Steven A. Maxwell Ph.D. & Jack A. Roth M.D.

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Mukhopadhyay, T., Maxwell, S.A., Roth, J.A. (1995). Wild-Type versus Mutant p53 . In: p53 Suppressor Gene. Molecular Biology Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-22275-1_3

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