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p53 pp 19–35Cite as

Lessons on p53 from Mouse Models

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Part of the book series: Molecular Biology Intelligence Unit ((MBIU,volume 1))

Abstract

Mutations in the p53 gene are implicated in the development of at least half of all human cancers, of a wide variety of types.1,2 This high incidence of mutations suggests that there exists a strong selection pressure for p53 inactivation during tumorigenesis. The idea that p53 mutations are important for tumor development in humans has also been supported by the finding that in the Li-Fraumeni syndrome, individuals inherit a mutant p53 allele and show a predisposition to developing a wide variety of cancers.3 An unambiguous cause and effect relationship, however, between p53 mutation and tumorigenesis has been clearly provided through the generation and analysis of p53 knockout mice.4–6 p53 null mice are subject to tumorigenesis at 100% frequency, indicating that the presence of p53 is crucial for preventing cancer development. In addition to this initial observation, significant understanding of the role of p53 as a tumor suppressor has come through further analysis of the p53 knockout mouse as well as other versions of mice with altered p53 genes. In this chapter, we will summarize various p53 knockout and knock-in models and how these models have helped us to understand p53 function in vivo.

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References

  1. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253(5015):49–53.

    PubMed  CAS  Google Scholar 

  2. Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 54(18):4855–4878.

    PubMed  CAS  Google Scholar 

  3. 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(4985):1233–1238.

    PubMed  CAS  Google Scholar 

  4. Donehower LA, Harvey M, Slagle BL et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356(6366):215–221.

    PubMed  CAS  Google Scholar 

  5. Jacks T, Remington L, Williams BO et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol 1994; 4(1):1–7.

    PubMed  CAS  Google Scholar 

  6. Purdie CA, Harrison DJ, Peter A et al. Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene. Oncogene 1994; 9(2):603–609.

    PubMed  CAS  Google Scholar 

  7. Mowat M, Cheng A, Kimura N et al. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature 1985; 314(6012):633–636.

    PubMed  CAS  Google Scholar 

  8. Ben-David Y, Bernstein A. Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell 1991; 66(5):831–834.

    PubMed  CAS  Google Scholar 

  9. Lavigueur A, Maltby V, Mock D et al. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol 1989; 9(9):3982–3991.

    PubMed  CAS  Google Scholar 

  10. Lee JM, Abrahamson JL, Kandel R et al. Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53 deficient mice. Oncogene 1994; 9(12):3731–3736.

    PubMed  CAS  Google Scholar 

  11. Harvey M, Vogel H, Morris D et al. A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. Nat Genet 1995; 9(3):305–311.

    PubMed  CAS  Google Scholar 

  12. Donehower L.A, Harvey M, Vogel H et al. Effects of genetic background on tumorigenesis in p53-deficient mice. Mol Carcinog 1995; 14(1):16–22.

    PubMed  CAS  Google Scholar 

  13. Harvey M, McArthur MJ, Montgomery CA Jr et al. Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice. Nat Genet 1993; 5(3):225–229.

    PubMed  CAS  Google Scholar 

  14. Venkatachalam S, Shi YP, Jones SN et al. Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J 1998; 17(16):4657–4667.

    PubMed  CAS  Google Scholar 

  15. Venkatachalam S, Tyner SD, Pickering CR et al. Is p53 haploinsufficient for tumor suppression? Implications for the p53+/-mouse model in carcinogenicity testing. Toxicol Pathol 2001; 29:147–154.

    PubMed  CAS  Google Scholar 

  16. Harvey M, McArthur MJ, Montgomery CA Jr et al. Genetic background alters the spectrum of tumors that develop in p53-deficient mice. FASEB J 1993; 7(10):938–943.

    PubMed  CAS  Google Scholar 

  17. Ullrich RL, Bowles ND, Satterfield LC, Davis CM. Strain-dependent susceptibility to radiation-induced mammary cancer is a result of differences in epithelial cell sensitivity to transformation. Radiat Res 1996; 146(3):353–355.

    PubMed  CAS  Google Scholar 

  18. Kuperwasser C, Hurlbut GD, Kittrell FS et al. Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome. Am J Pathol 2000; 157(6):2151–2159.

    PubMed  CAS  Google Scholar 

  19. Vousden KH, Lu X. Live or let die: the cell’s response to p53. Nat Rev Cancer 2002; 2(8):594–604.

    PubMed  CAS  Google Scholar 

  20. Kemp CJ, Wheldon T, Balmain A. p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nat Genet 1994; 8(1):66–69.

    PubMed  CAS  Google Scholar 

  21. Ruggeri B, Caamano J, Goodrow T et al. Alterations of the p53 tumor suppressor gene during mouse skin tumor progression. Cancer Res 1991; 51(24):6615–6621.

    PubMed  CAS  Google Scholar 

  22. Ruggeri B, DiRado M, Zhang SY et al. Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene. Proc Natl Acad Sci USA 1993; 90(3):1013–1017.

    PubMed  CAS  Google Scholar 

  23. Kemp CJ, Donehower LA, Bradley A, Balmain A. Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors. Cell 1993; 74(5):813–822.

    PubMed  CAS  Google Scholar 

  24. Clarke AR, Purdie CA, Harrison DJ et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 1993; 362(6423):849–852.

    PubMed  CAS  Google Scholar 

  25. Lowe SW, Schmitt EM, Smith SW et al. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 1993; 362(6423):847–849.

    PubMed  CAS  Google Scholar 

  26. Bosma MJ, Carroll AM. The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol 1991; 9:323–350.

    PubMed  CAS  Google Scholar 

  27. Bogue MA, Zhu C, Aguilar-Cordova E et al. p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes Dev 1996; 10(5):553–565.

    PubMed  CAS  Google Scholar 

  28. Guidos CJ, Williams CJ, Grandal I et al. V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors. Genes Dev 1996; 10(16):2038–2054.

    PubMed  CAS  Google Scholar 

  29. Nacht M, Strasser A, Chan YR et al. Mutations in the p53 and SCID genes cooperate in tumorigenesis. Genes Dev 1996; 10(16):2055–2066.

    PubMed  CAS  Google Scholar 

  30. Gurley KE, Vo K, Kemp CJ. DNA double-strand breaks, p53, and apoptosis during lymphomagenesis in scid/scid mice. Cancer Res 1998; 58(14):3111–3115.

    PubMed  CAS  Google Scholar 

  31. Difilippantonio MJ, Zhu J, Chen HT et al. DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. Nature 2000; 404(6777):510–514.

    PubMed  CAS  Google Scholar 

  32. Gao Y, Ferguson DO, Xie W et al. Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development. Nature 2000; 404(6780):897–900.

    PubMed  CAS  Google Scholar 

  33. Frank KM, Sharpless NE, Gao Y et al. DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. Mol Cell 2000; 5(6):993–1002.

    PubMed  CAS  Google Scholar 

  34. Lim DS, Vogel H, Willerford DM et al. Analysis of ku80-mutant mice and cells with deficient levels of p53. Mol Cell Biol 2000; 20(11):3772–3780.

    PubMed  CAS  Google Scholar 

  35. Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu Rev Biochem 2002; 71:101–132.

    PubMed  CAS  Google Scholar 

  36. Nacht M, Jacks T. V(D)J recombination is not required for the development of lymphoma in p53-deficient mice. Cell Growth Differ 1998; 9(2):131–138.

    PubMed  CAS  Google Scholar 

  37. Zhu C, Mills KD, Ferguson DO et al. Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell 2002; 109(7):811–821.

    PubMed  CAS  Google Scholar 

  38. Li B, Rosen JM, McMenamin-Balano J et al. neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic mice. Mol Cell Biol 1997; 17(6):3155–3163.

    PubMed  CAS  Google Scholar 

  39. Donehower LA, Godley LA, Aldaz CM et al. Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev 1995; 9(7):882–895.

    PubMed  CAS  Google Scholar 

  40. Hundley JE, Koester SK, Troyer DA et al. Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient in p53. Mol Cell Biol 1997; 17(2):723–731.

    PubMed  CAS  Google Scholar 

  41. Curtis DJ, Robb L, Strasser A, Begley CG. The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice. Oncogene 1997; 15(24):2975–2983.

    PubMed  CAS  Google Scholar 

  42. Marin MC, Hsu B, Meyn RE et al. Evidence that p53 and bcl-2 are regulators of a common cell death pathway important for in vivo lymphomagenesis. Oncogene 1994; 9(11):3107–3112.

    PubMed  CAS  Google Scholar 

  43. Harvey M, Vogel H, Lee EY et al. Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin. Cancer Res 1995; 55(5):1146–1151.

    PubMed  CAS  Google Scholar 

  44. Williams BO, Remington L, Albert DM et al. Cooperative tumorigenic effects of germline mutations in Rb and p53. Nat Genet 1994; 7(4):480–484.

    PubMed  CAS  Google Scholar 

  45. Halberg RB, Katzung DS, Hoff PD et al. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers. Proc Natl Acad Sci USA 2000; 97(7):3461–3466.

    PubMed  CAS  Google Scholar 

  46. Cichowski K, Shih TS, Schmitt E et al. Mouse models of tumor development in neurofibromatosis type 1. Science 1999; 286(5447):2172–2176.

    PubMed  CAS  Google Scholar 

  47. Reilly KM, Loisel DA, Bronson RT et al. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet 2000; 26(1):109–113.

    PubMed  CAS  Google Scholar 

  48. McClatchey AI, Saotome I, Mercer K et al. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 1998; 12(8):1121–1133.

    PubMed  CAS  Google Scholar 

  49. Wetmore C, Eberhart DE, Curran T. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res 2001; 61(2):513–516.

    PubMed  CAS  Google Scholar 

  50. Xu X, Wagner KU, Larson D et al. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet 1999; 22(1):37–43.

    PubMed  CAS  Google Scholar 

  51. Jonkers J, Meuwissen R, van der Gulden H et al. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 2001; 29(4):418–425.

    PubMed  CAS  Google Scholar 

  52. Clarke AR, Cummings MC, Harrison DJ. Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. Oncogene 1995; 11(9):1913–1920.

    PubMed  CAS  Google Scholar 

  53. Artandi SE. Telomere shortening and cell fates in mouse models of neoplasia. Trends Mol Med 2002; 8(1):44–47.

    PubMed  CAS  Google Scholar 

  54. Chin L, Artandi SE, Shen Q et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 1999; 97(4):527–538.

    PubMed  CAS  Google Scholar 

  55. Artandi SE, Chang S, Lee SL et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 2000; 406(6796):641–645.

    PubMed  CAS  Google Scholar 

  56. O’Hagan RC, Chang S, Maser RS et al. Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell 2002; 2(2):149–155.

    PubMed  Google Scholar 

  57. Marino S, Vooijs M, van Der Gulden H et al. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev 2000; 14(8):994–1004.

    PubMed  CAS  Google Scholar 

  58. Chen Z, Trotman LC, Shaffer D et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 2005; 436(7051):725–730.

    PubMed  CAS  Google Scholar 

  59. Meuwissen R, Linn SC, Linnoila RI et al. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 2003; 4(3):181–189.

    PubMed  CAS  Google Scholar 

  60. Morton JP, Klimstra DS, Mongeau ME, Lewis BC. Trp53 deletion stimulates the formation of metastatic pancreatic tumors. Am J Pathol 2008; 172(4):1081–1087.

    PubMed  Google Scholar 

  61. Quinn BA, Brake T, Hua X et al. Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53. PLoS One 2009; 4(12):e8404.

    PubMed  Google Scholar 

  62. Clark-Knowles KV, Senterman MK, Collins O, Vanderhyden BC. Conditional inactivation of Brca1, p53 and Rb in mouse ovaries results in the development of leiomyosarcomas. PLoS One 2009; 4(12):e8534.

    PubMed  Google Scholar 

  63. Soussi T. p53 alterations in human cancer: more questions than answers. Oncogene 2007; 26:2145–2156.

    PubMed  CAS  Google Scholar 

  64. Lang GA, Iwakuma T, Suh YA et al. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 2004; 119(6):861–872.

    PubMed  CAS  Google Scholar 

  65. Olive KP, Tuveson DA, Ruhe ZC et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004; 119(6):847–860.

    PubMed  CAS  Google Scholar 

  66. Armata HL, Garlick DS, Sluss HK. The ataxia telangiectasia-mutated target site Ser18 is required for p53-mediated tumor suppression. Cancer Res 2007; 67(24):11696–703.

    PubMed  CAS  Google Scholar 

  67. Chao C, Hergenhahn M, Kaeser MD et al. Cell type-and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses. J Biol Chem 2003; 278(42):41028–33.

    PubMed  CAS  Google Scholar 

  68. Sluss HK, Armata H, Gallant J, Jones SN et al. Phosphorylation of serine 18 regulates distinct p53 functions in mice. Mol Cell Biol 2004; 24(3):976–984.

    PubMed  CAS  Google Scholar 

  69. MacPherson D, Kim J, Kim T et al. Defective apoptosis and B-cell lymphomas in mice with p53 point mutation at Ser 23. EMBO J 2004; 23(18):3689–3699.

    PubMed  CAS  Google Scholar 

  70. Chao C, Herr D, Chun J, Xu Y. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J 2006; 25(11):2615–2622.

    PubMed  CAS  Google Scholar 

  71. Feng L, Hollstein M, Xu Y. Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence. Cell Cycle 2006; 5(23):2812–2819.

    PubMed  CAS  Google Scholar 

  72. Bruins W, Zwart E, Attardi LD et al. Increased sensitivity to UV radiation in mice with a p53 point mutation at Ser389. Mol Cell Biol 2004; 24(20):8884–8894.

    PubMed  CAS  Google Scholar 

  73. Feng L, Lin T, Uranishi H et al. Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity. Mol Cell Biol 2005; 25(13):5389–5395.

    PubMed  CAS  Google Scholar 

  74. Krummel K.A, Lee CJ, Toledo F, Wahl GM. The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. Proc Natl Acad Sci USA 2005; 102(29):10188–93.

    PubMed  CAS  Google Scholar 

  75. Chao C, Wu Z, Mazur SJ et al. Acetylation of mouse p53 at lysine 317 negatively regulates p53 apoptotic activities after DNA damage. Mol Cell Biol 2006; 26(18):6859–6869.

    PubMed  CAS  Google Scholar 

  76. Tang Y, Zhao W, Chen Y et al. Acetylation is indispensable for p53 activation. Cell 2008; 133(4):612–626.

    PubMed  CAS  Google Scholar 

  77. Toledo F, Krummel KA, Lee CJ et al. A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network. Cancer Cell 2006; 9(4):273–285.

    PubMed  CAS  Google Scholar 

  78. Toledo F, Lee CJ, Krummel KA et al. Mouse mutants reveal that putative protein interaction sites in the p53 proline-rich domain are dispensable for tumor suppression. Mol Cell Biol 2007; 27(4):1425–1432.

    PubMed  CAS  Google Scholar 

  79. Lin J, Chen J, Elenbaas B, Levine AJ. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994; 8(10):1235–1246.

    PubMed  CAS  Google Scholar 

  80. Johnson TM, Hammond EM, Giaccia A, Attardi LD. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Nat Genet 2005; 37(2):145–152.

    PubMed  CAS  Google Scholar 

  81. Johnson TM, Meade K, Pathak N et al. Knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence. Proc Natl Acad Sci USA 2008; 105(4):1215–1220.

    PubMed  CAS  Google Scholar 

  82. Broz DK, Attardi LD. In vivo analysis of p53 tumor suppressor function using genetically engineered mouse models. Carcinogenesis 2010; 31(8):1311–1318.

    Google Scholar 

  83. Luo JL, Yang Q, Tong WM et al. Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 2001; 20(3):320–328.

    PubMed  CAS  Google Scholar 

  84. Luo JL, Tong WM, Yoon JH et al. UV-induced DNA damage and mutations in Hupki (human p53 knock-in) mice recapitulate p53 hotspot alterations in sun-exposed human skin. Cancer Res 2001; 61(22):8158–8163.

    PubMed  CAS  Google Scholar 

  85. Tyner SD, Venkatachalam S, Choi J et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 2002; 415(6867):45–53.

    PubMed  CAS  Google Scholar 

  86. Rovinski B, Munroe D, Peacock J et al. Deletion of 5′-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation. Mol Cell Biol 1987; 7(2):847–853.

    PubMed  CAS  Google Scholar 

  87. Maier B, Gluba W, Bernier B et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev 2004; 18(3):306–319.

    PubMed  CAS  Google Scholar 

  88. Rudolph KL, Chang S, Lee HW et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999; 96(5):701–712.

    PubMed  CAS  Google Scholar 

  89. Garcia-Cao I, García-Cao M, Martín-Caballero J et al. «Super p53» mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 2002; 21(22):6225–6235.

    PubMed  CAS  Google Scholar 

  90. Matheu A, Maraver A, Klatt P et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 2007; 448(7151):375–379.

    PubMed  CAS  Google Scholar 

  91. Mendrysa SM, O’Leary KA, McElwee MK et al. Tumor suppression and normal aging in mice with constitutively high p53 activity. Genes Dev 2006; 20(1):16–21.

    PubMed  CAS  Google Scholar 

  92. Attardi LD, Jacks T. The role of p53 in tumour suppression: lessons from mouse models. Cell Mol Life Sci 1999; 55(1):48–63.

    PubMed  CAS  Google Scholar 

  93. Jones JM, Attardi L, Godley LA et al. Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis. Cell Growth Differ 1997; 8(8):829–838.

    PubMed  CAS  Google Scholar 

  94. Liu G, Parant JM, Lang G et al. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nat Genet 2004; 36(1):63–68.

    PubMed  CAS  Google Scholar 

  95. Braig M, Lee S, Loddenkemper C et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436(7051):660–665.

    PubMed  CAS  Google Scholar 

  96. Michaloglou C, Vredeveld LC, Soengas MS et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 2005; 436(7051):720–724.

    PubMed  CAS  Google Scholar 

  97. Collado M, Gil J, Efeyan A et al. Tumour biology: senescence in premalignant tumours. Nature 2005; 436(7051):642.

    PubMed  CAS  Google Scholar 

  98. Barboza JA, Liu G, Ju Z et al. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 2006; 103(52):19842–7.

    PubMed  CAS  Google Scholar 

  99. Cosme-Blanco W, Shen MF, Lazar AJ et al. Telomere dysfunction suppresses spontaneous tumori-genesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 2007; 8(5):497–503.

    PubMed  CAS  Google Scholar 

  100. Schmitt CA, McCurrach ME, de Stanchina E et al. INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev 1999; 13(20):2670–2677.

    PubMed  CAS  Google Scholar 

  101. Schmitt CA, Fridman JS, Yang M et al. Dissecting p53 tumor suppressor functions in vivo. Cancer Cell 2002; 1(3):289–298.

    PubMed  CAS  Google Scholar 

  102. Symonds H, Krall L, Remington L et al. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 1994; 78(4):703–711.

    PubMed  CAS  Google Scholar 

  103. Martins CP, Brown-Swigart L, Evan GI. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127:1323–1334.

    PubMed  CAS  Google Scholar 

  104. Xue W, Zender L, Miething C et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445:656–660.

    PubMed  CAS  Google Scholar 

  105. Ventura A, Kirsch DG, McLaughlin ME et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007; 445:661–665.

    PubMed  CAS  Google Scholar 

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    Laura D. Attardi

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Jiang, D., Attardi, L.D. (2010). Lessons on p53 from Mouse Models. In: p53. Molecular Biology Intelligence Unit, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8231-5_2

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