Advertisement

The role of p53 in malignancy

  • F. J. Keith
  • N. H. Russell
Part of the Cancer Treatment and Research book series (CTAR, volume 84)

Abstract

Mutations in the p53 gene are currently the most common genetic lesion found in human cancers [1,2]. The p53 protein was initially discovered in coprecipitation studies with SV40 large T antigen [3], with which p53 forms a stable complex [4]. Initial studies linked mutations in p53 to malignant transformation and culture cell immortalization [5–7], and thus it was shown that the p53 gene was a tumor suppressor gene [8,9]. The p53 gene is expressed at low levels in normal cells of the body, with the highest levels being found in the testes, ovary, thymus, and spleen [10]. The levels of p53 protein rise due to an alteration in its half-life [11], in response to DNA damage by a variety of agents including irradiation, chemical carcinogens, and tumor viruses. The major function of these elevated levels of p53 protein is to prevent propogation of cells with damaged DNA and thus prevent the onset of cancer. It has been shown that wild-type p53 achieves this by causing G1 arrest of the cell cycle [12] and so allowing either repair of the damaged DNA or, in cases of high DNA damage, the onset of apoptosis [13]. Thus p53 acts as a ‘guardian of the genome’ [14] and is vital to maintenance of DNA integrity. It is therefore evident that mutations in such a crucial gene are disastrous for the cell, since further lesions in the genome are tolerated and the chance of malignant transformation increases [15].

Keywords

Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Follicular Lymphoma Chronic Lymphatic Leukemia Hematopoetic Cell 
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.
    Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991). p53 mutations in human cancers. Science 253:49–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Levine AJ, Momand J, Finlay CA (1991). The p53 tumour suppressor gene. Nature 351:453.PubMedCrossRefGoogle Scholar
  3. 3.
    Lane DP, Crawford LV (1979). T antigen is bound to a host protein in SV40 transformed cells. Nature 278:261–263.PubMedCrossRefGoogle Scholar
  4. 4.
    Linzer DIH, Levine AJ (1979). Characterization of a 54 Kdalton cellular SV40 tumor antigen present in SV40 transformed cells and uninfected embryonal carcinoma cells. Cell 17:43–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Eliyahu D, Raz A, Gruss P, Givol D, Oren M (1984). Participation of p53 cellular tumor antigen in transformation of normal embryonic cells. Nature 312:646–649.PubMedCrossRefGoogle Scholar
  6. 6.
    Parada LF, Land H, Weinberg RA, Wolf D, Rotter V (1984). Cooperation between the gene encoding p53 tumor antigen and ras in cellular transformation. Nature 312:649–651.PubMedCrossRefGoogle Scholar
  7. 7.
    Jenkins JR, Rudge K, Currie GA (1984). Cellular immortalization by a cDNA clone encoding the transformation associated phosphoprotein p53. Nature 312:651–654.PubMedCrossRefGoogle Scholar
  8. 8.
    Finlay CA, Hinds WP, Levine AJ (1989). The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093.PubMedCrossRefGoogle Scholar
  9. 9.
    Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M (1989). Wild-type p53 can inhibit oncogene mediated focus formation. Proc Natl Acad Sci USA 86:8763–8767.PubMedCrossRefGoogle Scholar
  10. 10.
    Rogel A, Popliker M, Webb CG, Oren M (1985). p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues embryos and tumors. Mol Cell Biol 5:2851–2855.PubMedGoogle Scholar
  11. 11.
    Maltzman W, Czyzyk L (1982). Uv irradition stimulates levels of p53 cellular tumour antigen in non-transformed mouse cells. Mol Cell Biol 4:1689–1694.Google Scholar
  12. 12.
    Kastan MB, Onyekuere O, Sidransky D (1991). Participation of p53 in the cellular response to DNA damage. Cancer Res 51:6304–6311.PubMedGoogle Scholar
  13. 13.
    Yonish-Rouach O, 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Lane D (1992). p53: Guardian of the genome. Nature 358:15–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221.PubMedCrossRefGoogle Scholar
  16. 16.
    Wattel E, Preudhomme C, Hecquet B, Vanrumbeke M, Quesnel B, Dervite I, Morel P, Fenaux P (1994). p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 84:3148–3157.PubMedGoogle Scholar
  17. 17.
    Hsiao M, Yu A, Ku D (1994). Non-hereditary p53 mutations in T-cell acute lymphatic leukemia are associated with relapse phase. Blood 83:2922–2930.PubMedGoogle Scholar
  18. 18.
    Diccianni MB, Yu J, Hsiao M, Mukherjee S, Shao L-E, Yu AL (1994). Clinical significance of p53 mutations in relapsed T-cell acute lyphoblastic leukemia. Blood 84:3105–3112.PubMedGoogle Scholar
  19. 19.
    Lotem J, Sachs L (1993). Hematopoietic cells from mice deficient in wild-type p53 are more resistant to induction of apoptosis by some agents. Blood 82:1092–1096.PubMedGoogle Scholar
  20. 20.
    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
  21. 21.
    Neri A, Baldini L, Trecca D, Cro L, Polli E, Maiolo AT (1993). p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy. Blood 81:128–135.PubMedGoogle Scholar
  22. 22.
    El Rouby S, Thomas A, Costin D, Rosenberg CR, Potmesil M, Silber R, Newcomb EW (1993). p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression. Blood 82:3452–3459.PubMedGoogle Scholar
  23. 23.
    Saitoh S, Cunningham J, De Vries EM, et al. (1994). p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis. Oncogene 9:2869–2876.PubMedGoogle Scholar
  24. 24.
    Benchimol S, Lamb P, Crawford LV, Sheer D, Shours TB, Bruns GAP, Peacock J (1985). Transformation associated p53 protein is encoded by a gene on human chromosome 17. Somat Cell Mol Genet 11:505–509.PubMedCrossRefGoogle Scholar
  25. 25.
    McBride OW, Merry D, Givol D (1986). The gene for human p53 cellular tumour antigen is located on chromosome 17 short arm (17pl3). Proc Natl Acad Sci USA 83:130–134.PubMedCrossRefGoogle Scholar
  26. 26.
    Miller C, Mohandas T, Wolf D, Prokocimer M, Rotter V, Koeffler HP (1986). Human p53 gene localized to short arm of chromosome 17. Nature 319:783–784.PubMedCrossRefGoogle Scholar
  27. 27.
    Isobe M, Emanuel BS, Givol D, Oren M, Croce CM (1986). Localization of gene for human p53 tumour antigen to band 17p13. Nature 320:84–85.PubMedCrossRefGoogle Scholar
  28. 28.
    Zakut-Houri R, Bienz-Tadmor B, Givol D, Oren M (1985). Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. EMBO J 4:1251–1255.PubMedGoogle Scholar
  29. 29.
    Soussi T, Caron de Fromentel C, May P (1990). Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5:945–952.PubMedGoogle Scholar
  30. 30.
    Fields S, Jang SK (1990). Presence of a potent transcription activating sequence in the p53 protein. Science 249:1046–1049.PubMedCrossRefGoogle Scholar
  31. 31.
    Levine AJ, Perry ME, Chang A, Silver A, Dittmer D, Wu M, Welsh D (1994). The 1993 Walter Hubert lecture: The role of p53 tumour-suppressor gene in tumorigenesis. Br J Cancer 69:409–416.Google Scholar
  32. 32.
    Wang Y, Reed M, Wang P, Stenger JE, Mayr G, Anderson ME, Schwedes FJ, Tegtmeyer P (1993). p53 domains: identification and characterization of two autonomous DNA binding regions. Genes Dev 7:2575–2586.PubMedCrossRefGoogle Scholar
  33. 33.
    El-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B (1992). Human genomic DNA sequences define a consensus binding site for p53. Nature Genet 1:45–49.PubMedCrossRefGoogle Scholar
  34. 34.
    Maxwell SA, Roth JA (1993). Binding of cellular proteins to a conformational domain of tumour suppressor protein p53. Oncogene 8:3421–3424.PubMedGoogle Scholar
  35. 35.
    Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S (1994). Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci USA 91:6098–6102.PubMedCrossRefGoogle Scholar
  36. 36.
    Stenger J, Mayr G, Mann K, Tegtmeyer P (1992). Formation of stable p53 homotetramers and multiples of tetramers. Mol Carcinogen 5:102–106.CrossRefGoogle Scholar
  37. 37.
    Shaulsky G, Goldfinger N, Peled A, Rotter V (1991). Involvement of wild-type p53 protein in the cell cycle requires nuclear localization. Cell Growth Differ 2:661–667.PubMedGoogle Scholar
  38. 38.
    Sturzbecher HW, Maimets T, Chumakov P, et al. (1990). p53 interacts with p34cdc2 in mammalian cells: implication for cell cycle control and oncogenesis. Oncogene 5:795–801.PubMedGoogle Scholar
  39. 39.
    Yamaizumi M, Sugano T (1994). U.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle. Oncogene 9:2775–2784.PubMedGoogle Scholar
  40. 40.
    Kastan MB, Radin AI, Kuerbitz SJ, et al. (1991). Levels of p53 protein increase with maturation in human hematopoietic cells. Cancer Res 51:4279–4286.PubMedGoogle Scholar
  41. 41.
    Lowe SW, Schmitt EM, Smith GW, Osborne BA, Jacks T (1993). p53 is required for radiation induced apoptosis in mouse thymocytes. Nature 362:846–849.Google Scholar
  42. 42.
    Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH (1993). Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362:849–852.PubMedCrossRefGoogle Scholar
  43. 43.
    Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ Jr (1992). A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia telangiectasia. Cell 71:587–597.PubMedCrossRefGoogle Scholar
  44. 44.
    Fritsche M, Haessler C, Brander G (1993). Induction of nuclear acculation of the tumour suppressor protein p53 by DNA-damaging agents. Oncogene 8:307–318.PubMedGoogle Scholar
  45. 45.
    Lowe SW, Ruley HE, Jacks T, Houseman DE (1993). P53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967.PubMedCrossRefGoogle Scholar
  46. 46.
    Callahan R (1992). p53 mutations another breast cancer prognostic factor. J Natl Cancer Inst 84:826–827.PubMedCrossRefGoogle Scholar
  47. 47.
    Wang Y, Szekely L, Okan I, Klein G, Wiman KG (1993). Wild-type p53-triggered apoptosis is inhibited by bc1–2 in a v-myc-induced T-cell lymphoma line. Oncogene 8:3427–3431.PubMedGoogle Scholar
  48. 48.
    Chiou S-K, Rao L, White E (1994). Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol 14:2556–2563.PubMedGoogle Scholar
  49. 49.
    Ryan JJ, Prochownik E, Gottlieb CA, Apel IJ, Merino R, Nunez G, Clarke MF (1994). c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. Proc Natl Acad Sci USA 91:5878–5882.PubMedCrossRefGoogle Scholar
  50. 50.
    Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC (1994). Tumour suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799–1805.PubMedGoogle Scholar
  51. 51.
    Selvakumaran M, Lin H-K, Miyashita T, Wang HG, Krajewski S, Reed JC, Hoffman B, Liebermann D (1994). Immediate early up-regulation of bax expression by p53 but not TGFB1: a paradigm for distinct apoptotic pathways. Oncogene 9:1791–1798.PubMedGoogle Scholar
  52. 52.
    Haldar S, Negrini M, Monne M, Sabbioni S, Croce CM (1994). Down-regulation of bcl-2 by p53 in breast cancer cells. Cancer Res 54:2095–2097.PubMedGoogle Scholar
  53. 53.
    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
  54. 54.
    Steinmeyer K, Deppert W (1988). DNA binding properties of murine p53. Oncogene 3:501–506.PubMedGoogle Scholar
  55. 55.
    Farmer GE, Bargonetti J, Zhu H, Friedman P, Prywes R, Prives C (1992). Wild-type p53 activates transcription in vitro. Nature 358:83–86.PubMedCrossRefGoogle Scholar
  56. 56.
    Deb SP, Munoz RM, Brown DR, Subler MA, Deb S (1994). Wild-type human p53 activates the human epidermal growth factor receptor promoter. Oncogene 9:1341–1349.PubMedGoogle Scholar
  57. 57.
    Zambetti GP, Levine AJ (1993). A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855–865.PubMedGoogle Scholar
  58. 58.
    Ginsberg D, Mechta F, Yaniv M, Oren M (1991). Wild-type p53 can down-modulate the activity of various promotors. Proc Natl Acad Sci USA 88:9979–9983.PubMedCrossRefGoogle Scholar
  59. 59.
    Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245.PubMedCrossRefGoogle Scholar
  60. 60.
    Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992). Amplification of a gene encoding a p53 associated protein in human sarcomas. Nature 358:80–83.PubMedCrossRefGoogle Scholar
  61. 61.
    Barak Y, Oren M (1992). Enhanced binding of a 95kDa protein to p53 in cells undergoing p53 mediated growth arrest. EMBO J 11:2115–2121.PubMedGoogle Scholar
  62. 62.
    El-Deiry WS, Tokino T, Velculescu VE, et al. (1993). WAF1, a potential mediator of p53 tumour suppression. Cell 75:817–825.PubMedCrossRefGoogle Scholar
  63. 63.
    El-Deiry WS, Harper JW, O’Connor PM, et al. (1994). WAF1/CIP1 is induced in p53-mediated Gl arrest and apoptosis. Cancer Res 54:1169–1174.PubMedGoogle Scholar
  64. 64.
    Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ (1993). The p21 CDK-interacting protein CIP1 is a potent inhibitor of Gl cyclin-dependent kinases. Cell 75:805–816.PubMedCrossRefGoogle Scholar
  65. 65.
    Juven T, Barak Y, Zauberman A, George DL, Oren M (1993). Wild-type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene 8:3411–3416.PubMedGoogle Scholar
  66. 66.
    Wu X, Bayle JH, Olson D, Levine AJ (1993). The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7:1126–1132.PubMedCrossRefGoogle Scholar
  67. 67.
    Picksley SM, Vojtesek B, Sparks A, Lane DP (1994). Immunochemical analysis of the interaction of p53 with MDM2; fine mapping of the MDM-2 binding site on p53 using synthetic peptides. Oncogene 9:2523–2529.PubMedGoogle Scholar
  68. 68.
    Marston NJ, Crook T, Vousden KH (1994). Interaction of p53 with MDM-2 is independent of E6 and does not mediate wild type transformation suppressor function. Oncogene 9: 2707–2716.PubMedGoogle Scholar
  69. 69.
    Gannon JV, Greaves R, Iggo R, Lane DP (1990). Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 9:1595–1602.PubMedGoogle Scholar
  70. 70.
    Milner J, Medcalf EA (1991). Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 65:765–774.PubMedCrossRefGoogle Scholar
  71. 71.
    Cook A, Milner J (1990). Evidence for allosteric varients of wild-type p53, a tumour suppressor protein. Br J Cancer 61:548–552.PubMedCrossRefGoogle Scholar
  72. 72.
    Milner J, Watson JV (1990). Addition of fresh medium induces cell cycle and conformation changes in p53, a tumour suppressor protein. Oncogene 5:1683–1690.PubMedGoogle Scholar
  73. 73.
    Milner J (1984). Different forms of p53 detected by monoclonal antibodies in non-dividing and dividing lymphocytes. Nature 310:143–145.PubMedCrossRefGoogle Scholar
  74. 74.
    Michalovitz D, Halevy O, Oren M (1990). Conditional inhibition of transformation and of cell proliferation by a temperature sensitive mutan of p53. Cell 62:671–680.PubMedCrossRefGoogle Scholar
  75. 75.
    Milner J, Medcalf EA (1990). Temperature dependent switching between wild-type and mutant forms of p53-Vall35. J Mol Biol 216:481–484.PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang W, Guo X-Y, Hu G-Y, Liu W-B, Shay JW, Deisseroth AB (1994). A temperature sensitive mutant of human p53. EMBO J 13:2535–2544.PubMedGoogle Scholar
  77. 77.
    Rivas CI, Wisniewsky D, Strife A, Perz A, Lambek C, Bruno S, Darzynkiewicz Z, Clarkson N (1992). Constitutive expression of p53 protein in enriched normal human marrow blast cell population. Blood 79:1982–1986.PubMedGoogle Scholar
  78. 78.
    Zhang W, Hu G, Estey E, Hester J, Deisseroth A (1992). Altered conformation of the p53 protein in myeloid leukemia cells and mitogen-stimulated normal blood cells. Oncogene 7:1645–1647.PubMedGoogle Scholar
  79. 79.
    Zhu Y-M, Bradbury DA, Russell NH (1994). Wild-type p53 is required for apoptosis induced by growth factor deprivation in factor-dependent leukaemic cells. Br J Cancer 69: 468–472.PubMedCrossRefGoogle Scholar
  80. 80.
    Bradbury D, Zhu Y-M, Russell N (1994). Regulation of bcl–2 expression and apoptosis in acute myeloblastic leukaemia cells by granulocyte-macrophage colony-stimulating factor. Leukaemia 8:786–791.Google Scholar
  81. 81.
    Zhu Y-M, Bradbury D, Russell N (1993). Expression of different conformations of p53 in the blast cells of acute myeloblastic leukaemia is related to in vitro growth characteristics. Br J Cancer 68:851–855.PubMedCrossRefGoogle Scholar
  82. 82.
    Wernes BA, Levine AJ, Howley PM (1990). Association of human papillomavirus type 16 and 18 E6 protein with p53. Science 248:76–79.CrossRefGoogle Scholar
  83. 83.
    Mietz JA, Unger T, Huibregtse JM, Howley PM (1992). The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. EMBO J 11:5013–5020.PubMedGoogle Scholar
  84. 84.
    Finlay CA (1993). The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol Cell Biol 13:301–306.PubMedGoogle Scholar
  85. 85.
    Bueso-Ramos CE, Yang Y, deLeon E, McCown P, Stass SA, Albitar M (1993). The human MDM-2 oncogene is overexpressed in leukemias. Blood 82:2617–2623.PubMedGoogle Scholar
  86. 86.
    Goga A, McLaughlin J, Afar DEH, Sawyers CL, Witte ON (1994). Hematopoietic transformation by the bcr-abl tyrosine kinase is independent of its direct interaction with the grb2 adaptor molecule. Blood 84 (Suppl 1):513a.Google Scholar
  87. 87.
    Hall PA, Ray A, Lemoine NR, Midgley CA, Krausz T, Lane DP (1991). p53 immunostaining as a marker of malignant disease in diagnostic cytopathology. Lancet 338:513.PubMedCrossRefGoogle Scholar
  88. 88.
    Murakami Y, Hayashi K, Sekiya T (1991). Detection of aberrations of p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis. Cancer Res 51:3356–3361.PubMedGoogle Scholar
  89. 89.
    Orita M, Suzuki Y, Sekiya T, Hayashi K (1989). Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766–2770.PubMedCrossRefGoogle Scholar
  90. 90.
    Caron de Fromental C, Soussi T (1992). The p53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chrom Cancer 4:1–15.CrossRefGoogle Scholar
  91. 91.
    Buchman PM, Ninkina NN, Samarina OP, Georgiev GP (1988). Variation in the structure of the protein-coding region of the human p53 gene. Gene 70:245–252.PubMedCrossRefGoogle Scholar
  92. 92.
    Han K-A, Kulez-Martin MF (1992). Alternatively spliced p53 RNA in transformed and normal cells of different tissue types. Nucleic Acids Res 20:1979–1981.PubMedCrossRefGoogle Scholar
  93. 93.
    Lepelley P, Preudhomme C, Vanrumbeke M, Quesnel B, Cosson A, Fenaux P (1994). Detection of p53 mutations in hematological malignancies: comparison between immunocy-tochemistry and DNA analysis. Leukemia 8:1342–1349.PubMedGoogle Scholar
  94. 94.
    Nigro JM, Baker SJ, Preisinger AC, et al. (1989). Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708.PubMedCrossRefGoogle Scholar
  95. 95.
    Kocialkowski S, Pezzella F, Morrison H, Jones M, Laha S, Harris AL, Mason DY, Gatter KC (1995). Mutations in the p53 gene are not limited to classic ‘hot-spots’ and are not predictive of p53 protein expression in high-grade non-Hodgkins lymphoma. Br J Haematol 89:55–60.PubMedGoogle Scholar
  96. 96.
    Pignon JM, Vinatier I, Fanen P, Jonveaux P, Tournilhac O, Imbert M, Rochant H (1994). Exhaustive analysis of the p53 gene coding sequence by denaturing gradient gel electrophoresis: application to the detection of point mutations in acute leukemias. Hum Mutat 3:126–132.PubMedCrossRefGoogle Scholar
  97. 97.
    Lin J, Chen J, Elenbaas B, Levine AJ (1994). Several hydrophobic amino-acids in the p53 amino terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus-5 E1B 55kD protein. Genes Dev 8:1235–1246.PubMedCrossRefGoogle Scholar
  98. 98.
    Prives C (1994). How loops, B sheets and a helices help us to understand p53. Cell 78:543–546.PubMedCrossRefGoogle Scholar
  99. 99.
    Zhang W (1993). Novel DNA binding of p53 mutants and their role in transcriptional activation. Oncogene 8:2555–2559.PubMedGoogle Scholar
  100. 100.
    Unger T, Mietz JA, Scheffner M, Yee CL, Howley PM (1993). Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression. Mol Cell Biol 13:5186–5194.PubMedGoogle Scholar
  101. 101.
    Ory K, Legros Y, Augin C, Soussi T (1994). Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. EMBO J 13:3496–3504.PubMedGoogle Scholar
  102. 102.
    Zhang W, Shay JW, Deisseroth A (1993). Inactive p53 mutants may enhance the transcriptional activity of wild-type p53. Cancer Res 53:4772–4775.PubMedGoogle Scholar
  103. 103.
    Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC (1991). Mutational hotspots in the p53 gene in human hepatocellular carcinomas. Nature 350:427–428.PubMedCrossRefGoogle Scholar
  104. 104.
    Taylor JA, Watson MA, Devereux TR, Michels RY, Saccomanno G, Anderson M (1994). p53 mutation hotspot in radon-associated lung cancer. Lancet 343:86–87.Google Scholar
  105. 105.
    Walker RA, Dearing SJ, Lane DP, Varley JM (1991). Expression of the p53 protein in infiltrating and in situ breast carcinomas. J Pathol 165:203–211.PubMedCrossRefGoogle Scholar
  106. 106.
    Poller D, Hutchings CE, Galea M, Bell JA, Nicholson RA, Elston CW, Blarney RW, Ellis IO (1992). p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, cerB-2 protein overexpression and oestrogen receptor. Br J Cancer 66:538–588.Google Scholar
  107. 107.
    Ogden GR, Kiddie RA, Lunny DP, Lane DP (1992). Assessment of p53 protein expression in normal, benign and malignant oral mucosa. J Pathol 166:389–394.PubMedCrossRefGoogle Scholar
  108. 108.
    Starznska T, Bromley M, Ghosh A, Stern PL (1992). Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer 66:558–562.CrossRefGoogle Scholar
  109. 109.
    McLaren R, Kuzu I, Dunnill M, Harris A, Lane D, Gatter K (1992). The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer 66:735–738.PubMedCrossRefGoogle Scholar
  110. 110.
    Baker SJ, Fearon ER, Nigro JM, et al. (1989). Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221.PubMedCrossRefGoogle Scholar
  111. 111.
    Burns JE, Baird MC, Clark LJ, et al. (1993). Gene mutations and increased levels of p53 protein in human squamous cell carcinomas and their cell lines. Br J Cancer 67:1274–1289.PubMedCrossRefGoogle Scholar
  112. 112.
    Gannon JV, Lane P (1991). Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport. Nature 349:802–806.PubMedCrossRefGoogle Scholar
  113. 113.
    Sugimoto K, Toyoshima H, Sakai R, Miyagawa K, Hagiwara K, Ishikawa F, Takaku F, Yazaki Y, Hirai H (1992). Frequent mutations in the p53 gene in human myeloid leukemia cell lines. Blood 79:2378–2388.PubMedGoogle Scholar
  114. 114.
    Sugimoto K, Toyoshima H, Sakai R, Miyagawa K, Hagiwara K, Hirai H, Ishikawa F, Takaku F (1991). Mutations in the p53 gene in lymphoid leukemia. Blood 77:1153–1156.PubMedGoogle Scholar
  115. 115.
    Fenaux P, Jonveaux P, Quiquandon I, Lai JL, Pignon JM, Loucheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP (1991). p53 gene mutations in acute myeloid leukemia with 17p monosomy. Blood 78:1652–1657.PubMedGoogle Scholar
  116. 116.
    Hu G, Zhang W, Deisseroth AB (1992). p53 gene mutations in acute myelogenous leukaemia. Br J Haematol 81:489–494.PubMedCrossRefGoogle Scholar
  117. 117.
    Fenaux P, Preudhomme C, Quiquandon I, et al. (1992). Mutations of the p53 gene in acute myeloid leukaemia. Br J Haematol 80:178–183.PubMedGoogle Scholar
  118. 118.
    Imamura J, Miyoshi I, Koeffler HP (1994). p53 in hematologic malignancies. Blood 84: 2412–2421.PubMedGoogle Scholar
  119. 119.
    Wada H, Asada M, Nakazawa S, et al. (1994). Clonal expansion of p53 mutant cells in leukemia progression in vitro. Leukemia 8:53–59.PubMedGoogle Scholar
  120. 120.
    Trecca D, Longo L, Biondi A, Cro L, Calori R, Grigani F, Maiolo AT, Pelicci PG, Neri A (1994). Analysis of p53 mutations in acute myeloid leukemia. Am J Haematol 46:304–309.CrossRefGoogle Scholar
  121. 121.
    Ahuja H, Bareli M, Advani SH, Benchimol S, Cline MJ (1989). Alteration in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. Proc Natl Acad Sci USA 86:6783–6787.PubMedCrossRefGoogle Scholar
  122. 122.
    Kelman Z, Prokocimer M, Peller S, Kahn Y, Rechavi G, Manor Y, Cohen A, Rotter V (1989). Rearrangements in the p53 gene in Philadelphia chromosome positive chronic myelogenous leukemia. Blood 74:2318–2324.PubMedGoogle Scholar
  123. 123.
    McGahon A, Bissonnette R, Schmitt M, Cotter KM, Green DR, Cotter TG (1994). BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood 83:1179–1187.PubMedGoogle Scholar
  124. 124.
    Jonveaux PH, Fenaux P, Quiquandon I, Pignon JM, Lai JM, Loucheux-Lefebvre MH, Goossens M, Bauters F, Berger T (1991). Mutations in the p53 gene in myelodysplastic syndromes. Oncogene 6:2243–2247.PubMedGoogle Scholar
  125. 125.
    Sugimoto K, Hirano N, Toyoshima H, Cluiba S, Mano H, Takaku F, Yazaki Y, Hirai H (1993). Mutations of p53 gene in myelodysplastic syndrome and MDS-derived leukemia. Blood 81:3022–3026.PubMedGoogle Scholar
  126. 126.
    Chin KV, Ueda K, Pastan I, Gothesman MM (1992). Modulation of activity of the promoter of the human mdr1 gene by ras and p53. Science 255:459–462.PubMedCrossRefGoogle Scholar
  127. 127.
    Preudhomme C, Lepelley P, Vachee A, Soenan V, Quesnel B, Cosson A, Fenaux P (1993). Relationship between p53 gene-mutations and multidrug-resistance (mdrl) gene-expression in myelodysplastic syndromes. Leukemia 7:1888–1890.PubMedGoogle Scholar
  128. 128.
    Tsushita K, Hotta T, Ichikawa A, Saito H (1992). Mutation of p53 does not play a critical role in myelodysplastic syndrome and its transformation to acute leukaemia. Br J Haematol 81:456–457.PubMedCrossRefGoogle Scholar
  129. 129.
    Prokocimer M, Shaklai M, Ben-Basset H, Wolf D, Goldfinger N, Rotter V (1986). Expression of p53 in human leukemia and lymphoma. Blood 68:113–118.PubMedGoogle Scholar
  130. 130.
    Ichikawa A, Hotts T, Takagi N, Tsushita K, Kinoshita T, Nagai H, Murakami Y, Hayashi K, Saito H (1992). Mutations of p53 gene and their relation to disease progression in B-cell lymphoma. Blood 79:2701–2707.PubMedGoogle Scholar
  131. 131.
    Farrugia MM, Duan L-J, Reis MD, Ngan BY, Berinstein NL (1994). Alterations of the p53 tumour suppressor gene in diffuse large cell lymphomas with translocations of the c-MYC and BCL-2 proto-oncogenes. Blood 83:191–198.PubMedGoogle Scholar
  132. 132.
    Chang H, Benchimol S, Minden MD, Messner HA (1994). Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma. Blood 83:452–459.PubMedGoogle Scholar
  133. 133.
    Rodriguez MA, Ford RJ, Goodacre A, Selvanayagam P, Cabanillas F, Deisseroth AB (1991). Chromosome 17p and p53 changes in lymphoma. Br J Haematol 79:575–582.PubMedCrossRefGoogle Scholar
  134. 134.
    Lo Coco L, Gaidano G, Louie DC, Offit K, Chaganti RSK, Dallafavera R (1993). P53 mutations are associated with histologic transformation of follicular lymphoma. Blood 82:2289–2295.PubMedGoogle Scholar
  135. 135.
    Gupta RK, Norton RJ, Thompson IW, Lister TA, Bodner JG (1992). p53 expression in Reed-Sternberg cells of Hodgkins Disease. Br J Cancer 66:649–652.PubMedCrossRefGoogle Scholar
  136. 136.
    Gupta RK, Patel K, Bodmer WF, Bodmer JG (1993). Mutation of p53 in primary biopsy material and cell lines from Hodgkin disease. Proc Natl Acad Sci USA 90:2817–2821.PubMedCrossRefGoogle Scholar
  137. 137.
    Trumper LH, Brady G, Bagg A, et al. (1993). Single-cell analysis of Hodgkin and Reed-Sternberg cells: molecular heterogeneity of gene expression and p53 mutations. Blood 81:3097–3115.PubMedGoogle Scholar
  138. 138.
    Mazars GR, Portier M, Zhang XG, Jourdan M, Bataille R, Theillet C, Klein B (1992). Mutations of the p53 gene in human myeloma cell lines. Oncogene 7:1015–1018.PubMedGoogle Scholar
  139. 139.
    Corradini P, Inghirami G, Astolfl M, et al. (1994). Inactivation of tumour suppressor genes, p53 and Rb1, in plasma cell dyscrasias. Leukemia 8:758–768.PubMedGoogle Scholar
  140. 140.
    Gaidano G, Ballerini P, Gong JZ, Inghirami G, Neri A, Newcomb EW, Magrath IT, Knowles DM, Dalla-Favera R (1991). p53 mutations in human lymphoid malignancies: association with Burkitts lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci USA 88: 5413–5417.PubMedCrossRefGoogle Scholar
  141. 141.
    Zhang W, Cork A, Trujillo J, Calvert L, Hu G, Andersson B, Deisseroth AB (1993). Mutations of the p53 gene are associated with genetic instability and immortalization in myelogenous leukemia. Cancer Res Ther Control 3:139–144.Google Scholar
  142. 142.
    Gandini D, Cuneo A, Carli MG, Lanza F, Castold GL, Del Senno L (1994). Total loss of p53 DNA sequences in acute myeloid leukaemia. Leukemia Res 18:63–65.CrossRefGoogle Scholar
  143. 143.
    Hehlmann R, Heimpel H, Hasford J, et al. (1993). Randomised study of bisulphan and hydroxyurea in chronic myelogenous leukemia (CML): prolongation of survival by hydroxyurea. Blood 82:398–407.PubMedGoogle Scholar
  144. 144.
    Shiohara M, El-Deiry WS, Wada M, Nakamaki T, Takeuchi S, Yang R, Chen D-L, Vogelstein B, Koeffler HP (1994). Absence of WAF1 mutations in a variety of human malignancies. Blood 84:3781–3784.PubMedGoogle Scholar
  145. 145.
    Cheng J, Yeargin J, Friedman T, Hass M (1992). Suppression of acute lymphoblastic leukemia by the human wild-type p53 gene. Cancer Res 52:222–226.PubMedGoogle Scholar
  146. 146.
    Hupp TR, Meek DW, Midgely CA, Lane DP (1993). Regulation of the specific DNA-binding function of p53. Cell 71:875–876.CrossRefGoogle Scholar
  147. 147.
    Sturzbecher H-W, Brain R, Addison C, Rudge K, Remm M, Grimaldi M, Keenan E, Jenkins JR (1992). A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene 7:1513–1523.PubMedGoogle Scholar
  148. 148.
    Ullrich SJ, Anderson CW, Mercer WE, Appella E (1992). The p53 tumor suppressor protein, a modulator of cell proliferation. J Biol Chem 267:15259–15262.PubMedGoogle Scholar
  149. 149.
    Shaulsky G, Goldfinger N, Ben-Ze’ev A, Rotter V (1990). Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol 10:6565–6577.PubMedGoogle Scholar
  150. 150.
    Milner J (1991). A conformation hypothesis for the suppressor and promoter functions of p53 in cell growth control and in cancer. Proc R Soc Lond B 245:139–145.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1996

Authors and Affiliations

  • F. J. Keith
  • N. H. Russell

There are no affiliations available

Personalised recommendations