Murine tumor suppressor models

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 400, Issue 1-2, 1998, Pages 391-407

  Venkatachalam, Sundaresan ^a   Donehower, Lawrence A ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

APC; BRCA1; BRCA2; Gene targeting; INK4a; Knockout mouse; Mouse cancer model; NF1; NF2; p53; Rb; Tumor suppressor; VHL; WT 1

Indexed keywords

ANIMAL MODEL; ARTICLE; CANCER GENETICS; CANCER MODEL; CANCER SUSCEPTIBILITY; GENE MUTATION; GENE TARGETING; GENETIC SUSCEPTIBILITY; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR SUPPRESSOR GENE;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; GENES, TUMOR SUPPRESSOR; MICE; MICE, KNOCKOUT; MICE, MUTANT STRAINS; NEOPLASMS, EXPERIMENTAL; NEOPLASTIC SYNDROMES, HEREDITARY;

EID: 0032565573     PISSN: 00275107     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0027-5107(98)00018-9     Document Type: Article

References (149)

1. [1] M. Torres, The use of embryonic stem cells for the genetic manipulation of the mouse, Curr. Top. Dev. Biol. 36 (1998) 99-114.
2. [2] D.W. Melton, Gene targeting in the mouse, Bioessays 16 (1994) 633-638.
3. [3] M.R. Cappechi, Altering the genome by homologous recombination, Science 244 (1989) 1288-1292.
4. [4] M.M. Matzuk, M.J. Finegold, G.J. Su, A.J.W. Hsueh, A. Bradley, Alpha-inhibin is a tumor suppressor gene with gonadal specificity in mice, Nature 360 (1992) 313-319.
5. [5] L. Yamasaki, T. Jacks, R.T. Bronson, E. Goillot, E. Harlow, N.J. Dyson, Tumor induction and tissue atrophy in mice lacking E2F-1, Cell 85 (1996) 537-548.
6. [6] T. Jacks, Tumor suppressor gene mutations in mice, Annu. Rev. Genet. 30 (1996) 603-636.
7. [7] A. Bradley, Mutant mice in cancer research, Semin. Cancer Biol. 7 (1996) 227-299.
8. [8] B.O. Williams, T. Jacks, Mechanisms of carcinogenesis and the mutant mouse, Curr. Opin. Genet. Dev. 6 (1996) 65-70.
9. [9] S.N. Jones, L.A. Donehower, A. Bradley, Analysis of tumor suppressor genes using transgenic mice, Methods 8 (1995) 247-258.
10. [10] M.S. Greenblatt, W.P. Bennett, M. Hollstein, C.C. Harris, Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis, Cancer Res. 54 (1994) 4855-4878.
11. [11] D. Malkin, p53 and the Li-Fraumeni syndrome, Biochim. Biophys. Acta 1198 (1994) 197-213.
12. [12] F.P. Li, J.F. Fraumeni, Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?, Ann. Int. Med. 71 (1969) 747-752.
13. [13] W.G. Nelson, M.B. Kastan, DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage responses, Mol. Cell. Biol. 14 (1994) 1815-1823.
14. [14] D.S. Lim, P. Hasty, A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53, Mol. Cell. Biol. 16 (1996) 7133-7143.
15. [15] Yonish-Rouach, D. Resnitzky, J. Lotem, L. Sachs, A. Kimchi, M. Oren, Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6, Nature 352 (1991) 345-347.
16. [16] J.M. Ford, P.C. Hanawalt, Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV resistance, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 8876-8880.
17. [17] Y. Yin, M.A. Tainsky, F.Z. Bischoff, L.C. Strong, G.M. Wahl, Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53, Cell 70 (1992) 937-948.
18. [18] L.R. Livingstone, A. White, J. Sprouse, E. Livanos, T. Jacks, T.D. Tlsty, Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53, Cell 70 (1992) 605-620.
19. [19] L.J. Ko, C. Prives, p53: puzzle and paradigm, Genes Dev. 10 (1996) 1054-1072.
20. [20] A.J. Levine, p53, the cellular gatekeeper for growth and division, Cell 88 (1997) 323-331.
21. [21] L.A. Donehower, M. Harvey, B.L. Slagle, M.J. McArthur, S.A.J. Montgomery, J.S. Butel, A. Bradley, Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors, Nature (1992) 215-221.
22. [22] T. Jacks, L. Remington, B.O. Williams, E.M. Schmitt, S. Halachmi, R.T. Bronson, R.A. Weinberg, Tumor spectrum analysis in p53-mutant mice, Curr. Biol. 4 (1994) 1-7.
23. [23] T. Tsukada, Y. Tomooka, S. Takai, Y. Ueda, S. Nishikawa, T. Yagi, T. Tokunaga, N. Takeda, Y. Suda, S. Abe, I. Matsuo, I. Ikawa, S. Aizawa, Enhanced proliferative potential in culture of cells from p53-deficient mice, Oncogene 8 (1993) 3313-3322.
24. [24] C.A. Purdie, D.J. Harrison, A. Peter, L. Dobbie, S. White, S.E.M. Howie, D.M. Salter, C.C. Bird, A.H. Wyllie, M.L. Hooper, A.R. Clarke, Tumor incidence, spectrum and ploidy in mice with a large deletion in the p53 gene, Oncogene 9 (1994) 603-609.
25. [25] Y. Gondo, K. Nakamura, T. Sasaoka, K. Ito, M. Kimura, M. Katsuki, Gene replacement of the p53 gene with the lacZ gene in mouse embryonic cells and mice by using two steps of homologous recombination, Biochem. Biophys. Res. Commun. 202 (1994) 830-837.
26. [26] J.F. Armstrong, M.H. Kaufman, D.J. Harrison, A.R. Clarke, High frequency developmental abnormalities in p53-deficient mice, Curr. Biol. 5 (1995) 931-936.
27. [27] V.P. Sah, L. Attardi, G.J. Mulligan, B.O. Williams, R.T. Bronson, T. Jacks, A subset of p53-deficient embryos exhibit exencephaly, Nat. Genet. 10 (1995) 175-180.
28. [28] L.A. Donehower, L.A. Godley, C.M. Aldaz, R. Pyle, Y.P. Shi, D. Pinkel, J. Gray, A. Bradley, D. Medina, H. Varmus, Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability, Genes Dev. 9 (1995) 882-895.
29. [29] L.A. Donehower, The p53-deficient mouse: a model for basic and applied cancer studies, Sem. Cancer Biol. 7 (1996) 269-278.
30. [30] L.A. Donehower, M.J. McArthur, S.A.J. Montgomery, S.H. Park, T. Thompson, R.J. Ford, A. Bradley, Effects of genetic background on tumorigenesis in p53-deficient mice, Mol. Carcinog. 14 (1995) 16-22.
31. [31] C.J. Kemp, L.A. Donehower, A. Bradley, A. Balmain, Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors, Cell 74 (1993) 813-822.
32. [32] A. Zeigler, A.S. Jonason, D.J. Leffell, J.A. Simon, H.W. Sharma, J. Kimmelman, L. Remington, T. Jacks, D.E. Brash, Sunburn and p53 in the onset of skin cancer, Nature 372 (1994) 773-776.
33. [33] H. Symonds, L. Krail, L. Remington, M. Saenz-Robles, S. Lowe, T. Jacks, T. Van Dyke, p53-dependent apoptosis suppresses tumor growth and progression in vivo, Cell 78 (1994) 703-711.
34. [34] J.M. Jones, L. Attardi, L.A. Godley, R. Laucirica, D. Medina, T. Jacks, H. Varmus, L.A. Donehower, Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis, Cell Growth Diff. 8 (1997) 829-838.
35. [35] A.G. Knudson, Mutation and cancer: statistical study of retinoblastoma, Proc. Natl. Acad. Sci. U.S.A. 68 (1971) 820-823.
36. [36] A.G. Knudson, Hereditary cancer, oncogenes, and antioncogenes, Cancer Res. 45 (1985) 1437-1443.
37. [37] S. Lowe, E.S. Schmitt, S.W. Smith, B.A. Osborne, T. Jacks, p53 is required for radiation-induced apoptosis in mouse thymocytes, Nature 362 (1993) 847-849.
38. [38] A.R. Clarke, C.A. Purdie, D.J. Harrison, R.G. Morris, C.C. Bird, M.L. Hooper, A.H. Wyllie, Thymocyte apoptosis induced by p53-dependent and independent pathways, Nature 362 (1993) 849-852.
39. [39] M. Harvey, A. Sands, R.S. Weiss, M.E. Hegi, R.W. Wiseman, P. Pantazis, B.C. Giovanella, M.A. Tainsky, A. Bradley, L.A. Donehower, In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice, Oncogene 8 (1993) 2457-2467.
40. [40] S.M. Cross, C.A. Sanchez, C.A. Morgan, M.K. Schimke, S. Ramel, R.L. Idzerda, W.H. Raskind, B.J. Reid, A p53-dependent mouse spindle checkpoint, Science 267 (1995) 1353-1356.
41. [41] L.A. Donehower, Effects of p53 mutation on tumor progression: recent insights from mouse tumor models, Biochim. Biophys. Acta 1242 (1996) 171-176.
42. [42] B. Schwetz, D. Gaylor, New directions for predicting carcinogenesis, Mol. Carcinog. 20 (1997) 275-279.
43. [43] A.G. Knudson, The ninth Gordon Hamilton-Fairley memorial lecture. Hereditary cancers:clues to mechanisms of carcinogenesis, Br. J. Cancer 59 (1989) 661-666.
44. [44] D.J. Riley, E.Y.-H.P. Lee, W.H. Lee, The retinoblastoma protein: more than a tumor suppressor, Annu. Rev. Cell Biol. 10 (1994) 1-29.
45. [45] R.A. Weinberg, The retinoblastoma protein and the cell cycle, Cell 81 (1995) 323-330.
46. [46] T. Jacks, A. Fazeli, E.M. Schmitt, R.T. Bronson, M.A. Doodell, R.A. Weinberg, Effects of Rb mutation in the mouse, Nature 359 (1992) 295-300.
47. [47] E.Y.-H.P. Lee, C.Y. Chang, N. Hu, Y.C. Wang, C.C. Lai, K. Herrup, W.H. Lee, A. Bradley, Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis, Nature 359 (1992) 288-294.
48. [48] A.R. Clarke, E.R. Maandag, M.v. Roon, N.M.T. Van Lught, M. van der Valk, M.L. Hooper, A. Berns, H. Riele, Requirement for a functional Rb-1 gene in murine development, Nature 359 (1992) 328-330.
49. [49] N. Hu, A. Gutsmann, D.C. Herbert, A. Bradley, W.H. Lee, E.Y. Lee, Heterozygous Rb-1 delta 20/+ mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance, Oncogene 9 (1994) 1021-1027.
50. [50] M.R. Al-Ubaidi, R.L. Font, A.O. Quiambo, M.J. Keener, G. Liou, Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under the control of the human interphotoreceptor retinoid binding protein promoter, J. Cell. Biol. 119 (1992) 1681-1687.
51. [51] J.J. Windle, D.A. Albert, J.M. O'Brien, D.M. Marcus, C.M. Disteche, R. Bernards, P.L. Mellon, Retinoblastoma in transgenic mice, Nature 343 (1990) 665-668.
52. [52] A.K. Howes, N. Ransom, D.S. Papermaster, J.G.H. Lasudry, D.M. Albert, J.J. Windle, Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53, Genes Dev. 8 (1994) 1300-1310.
53. [53] B.O. Williams, L. Remington, D.M. Albert, S. Mukai, R.T. Bronson, T. Jacks, Cooperative tumorigenic effects of germline mutations in Rb and p53, Nat. Genet. 7 (1994) 480-484.
54. [54] M. Harvey, H. Vogel, E.Y.-H.P. Lee, A. Bradley, L.A. Donehower, Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin, Cancer Res. 55 (1995) 1146-1151.
55. [55] R.E. Herera, V.P. Sah, B.O. Williams, T.P. Makela, R.A. Weinberg, T. Jacks, Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts, Mol. Cell. Biol. 16 (1996) 2402-2407.
56. ink4a requires functional retinoblastoma protein, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6289-6293.
57. [57] S. Bulow, Familial polyposis coli, Dan. Med. Bull. 34 (1987) 1-15.
58. [58] J. Groden, A. Thliveris, W. Samowitz, M. Carlson, L. Gelbert, H. Albertsen, G. Joslyn, J. Stevens, L. Spirio, M. Robertson, Identification and characterization of the familial adenomatous polyposis coli gene, Cell 66 (1991) 589-600.
59. [59] K.W. Kinzler, M.C. Nilbert, L.K. Su, B. Vogelstein, T.M. Bryan, D.B. Levy, K.J. Smith, A.C. Preisinger, P. Hegde, D. McKechnie, Identification of FAP locus genes from chromosome 5q21, Science 253 (1991) 661-665.
60. [60] M. Ilyas, I.P.M. Tomlinson, The interactions of APC, E-Cadherin and B-catenin in tumor development and progression, J. Pathol. 182 (1997) 128-137.
61. [61] A.R. Moser, H.C. Pilot, W.F. Dove, A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse, Science 247 (1990) 322-324.
62. [62] A. Bilger, A.R. Shoemaker, K.A. Gould, W.F. Dove, Manipulation of the mouse germline in the study of Min-induced neoplasia, Sem. Cancer Biol. 7 (1997) 249-260.
63. [63] A.R. Moser, A.R. Shoemaker, C.S. Connelly, L. Clipson, K.A. Gould, C. Luongo, W.F. Dove, P.H. Siggers, H.P. Gardner, Homozygosity for the min allele of Apc results in disruption of mouse development prior to gastrulation, Dev. Dyn. 203 (1995) 422-433.
64. [64] C. Luongo, A.R. Moser, S. Gledhill, W.F. Dove, Loss of Apc in intestinal adenomas from Min mice, Cancer Res. 54 (1994) 5947-5952.
65. [65] A.R. Moser, E.M. Mattes, W.F. Dove, M.J. Lindstrom, J.D. Haag, M.N. Gould, ApcMin, a mutation in the murine Apc gene, predisposes to mammary carcinomas and focal alveolar hyperplasias, Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 8977-8981.
66. [66] M. Oshima, H. Oshima, K. Kitigawa, M. Kobayashi, C. Itakura, M.M. Taketo, Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 4482-4486.
67. [67] H. Shibata, K. Toyama, H. Shioya, M. Ito, M. Hirota, S. Hasegawa, H. Matsumoto, H. Takano, T. Akiyama, K. Toyoshima, R. Kanamaru, Y. Kanegae, I. Saito, Y. Nakamura, K. Shiba, T. Noda, Rapid colorectal adenoma formation initiated by conditional targeting of the APC gene, Science 278 (1997) 120-123.
68. [68] W.F. Dietrich, E.S. Lander, J.S. Smith, A.R. Moser, K.S. Gould, C. Luongo, N. Borenstein, W. Dove, Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse, Cell 75 (1993) 631-639.
69. [69] M. MacPhee, K.P. Chepenik, R.A. Liddell, K.K. Nelson, L.D. Siracusa, A.M. Buchberg, The secretory phospholipase A2 gene is a candidate for the Mom 1 locus, a major modifier of ApcMin-mduced intestinal neoplasia, Cell 81 (1995) 957-966.
70. [70] R. Cormier, K. Hong, R.B. Halberg, T.L. Hawkins, P. Richardson, R. Mulherkar, W.F. Dove, E.S. Lander, Secretory phospholipase Pla2g2a confers resistance to intestinal tumorgenesis, Nature Genet. 17 (1997) 88-91.
71. [71] A.R. Clarke, M.C. Cummings, D.J. Harrison, Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy, Oncogene 11 (1995) 1913-1920.
72. [72] Reitmar, J. Cai, M. Bjerknes, M. Redston, H. Cheng, M.T.L. Find, K. Hay, A. Mitri, B.V. Bapat, T.W. Mak, S. Gallinger, MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis, Cancer Res. 56 (1996) 2922-2926.
73. [73] M. Oshima, J.E. Dinchuk, S.L. Kargman, H. Oshima, B. Hancock, E. Kwong, J.M. Trzaskos, J.F. Evans, M.M. Taketo, Suppression of intestinal polyposis in Apc delta 716 knockout mice by inhibition of cyclooxygenase 2 (COX-2), Cell 87 (1996) 803-809.
74. [74] P.W. Laird, L. Jackson-Grusby, S. Dickinson, W.E. Jung, E. Li, R.A. Weinberg, R. Jaenisch, Suppression of intestinal neoplasia by DNA hypomethylation, Cell 81 (1995) 197-205.
75. [75] C.L. Wilson, L.M. Matrisian, Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions, Int. J. Biochem. Cell Biol. 28 (1996) 123-136.
76. [76] C.L. Wilson, K.J. Heppner, P.A. Labosky, B.L. Hogan, L.M. Matrisian, Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 1402-1407.
77. [77] M. Oshima, H. Oshima, M. Tsutsumi, S. Nishimura, T. Sugimura, M. Nagao, M.M. Taketo, Effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on intestinal polyp development in Apc delta 716 knockout mice, Mol. Carcinog. 15 (1996) 11-17.
78. [78] H. Oshima, M. Takahashi, M. Oshima, M. Tsutsumi, K. Yazawa, T. Sugimura, S. Nishimura, K. Wakabayashi, M.M. Taketo, Effects of docosahexaeonic acid (DHA) on intestinal polyp development in Apc delta 716 knockout mice, Carcinogenesis 16 (1995) 2605-2607.
79. [79] D.A. Stumph, Neurofibromatosis, Arch. Neurol. 45 (1988) 575-578.
80. [80] K. Cichowski, T.S. Shih, T. Jacks, Nf1 gene targeting: toward models and mechanisms, Sem. Cancer Biol. 7 (1996) 291-298.
81. [81] G.F. Xu, B. Lin, K. Tanaka, D. Dunn, D. Wood, R. Gesteland, R. White, R. Weiss, F. Tamanoi, The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants if S. cerevisiae, Cell 63 (1990) 835-841.
82. [82] J.E. DeClue, A.G. Papageorge, J.A. Fletcher, S.R. Diehl, W.C.R. Vass, D.R. Lowy, Abnormal regulation of p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis, Cell 69 (1992) 265-273.
83. [83] T. Jacks, T.S. Shih, E.M. Schmitt, R.T. Bronson, A. Bernards, R.A. Weinberg, Tumor predisposition in mice heterozygous for a targeted mutation in Nf1, Nat. Genet. 7 (1994) 353-361.
84. [84] C.I. Brannan, A.S. Perkins, K.S. Vogel, N. Ratner, M.L. Nordlund, S.W. Reid, A.M. Buchberg, N.A. Jenkins, L.F. Parada, N.G. Copeland, Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues, Genes Dev. 8 (1994) 1019-1029.
85. [85] G. Bollag, D.W. Clapp, S. Shih, F. Adler, Y.Y. Zhang, P. Thompson, B.J. Lange, M.H. Freedman, F. McCormick, T. Jacks, K. Shannon, Loss of NF1 results in activation of the Ras signalling pathway and leads to aberrant growth in haematopoietic cells, Nat. Genet. 12 (1996) 144-148.
86. [86] D.A. Largaespada, C.I. Brannan, N.A. Jenkins, N.G. Copeland, Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukemia, Nat. Genet. 12 (1996) 137-143.
87. [87] H.A. Kim, T. Rosenbaum, M.A. Marchionni, N. Ratner, J.E. DeClue, Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes, Oncogene 11 (1995) 325-335.
88. [88] T. Rosenbaum, Y.L. Boissy, K. Kombrinck, C.I. Brannan, N.A. Jenkins, N.G. Copeland, N. Ratner, Neurofibromin-deficient fibroblasts fail to form perineurium in vitro, Development 121 (1995) 3583-3592.
89. [89] K.S. Vogel, C.I. Brannan, N.A. Jenkins, N.G. Copeland, L.F. Parada, Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons, Cell 82 (1995) 733-742.
90. [90] A.G. Menon, K.M. Anderson, V.M. Riccardi, R.V. Chung, J.M. Whaley, D.W. Yandell, G.E. Farmer, R.N. Freiman, J.K. Lee, F.P. Li, Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 5435-5439.
91. [91] J.F. Gusella, V. Ramesh, M. MacCollin, L.B. Jacoby, Neurofibromatosis 2: loss of merlin's protective spell, Curr. Opin. Genet. Dev. 6 (1996) 87-92.
92. [92] I.F. Pollack, J.J. Mulvilhill, Neurofibromatosis 1 and 2, Brain Pathol. 7 (1997) 823-836.
93. [93] A.I. McClatchey, I. Saotome, V. Ramesh, J.F. Gusella, T. Jacks, The cytoskeletal-associated Nf2 tumor suppressor gene product is essential for mouse embryogenesis, Genes Dev. 11 (1997) 1250-1260.
94. [94] M. Serrano, G.J. Hannon, D. Beach, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4, Nature 366 (1993) 704-707.
95. [95] Y. Xiong, G.J. Hannon, H. Zhang, D. Casso, R. Kobayashi, D. Beach, p21 is a universal inhibitor of cyclin kinases, Nature 366 (1993) 701-704.
96. [96] A. Kamb, N.A. Gruis, J. Weaver-Feldhaus, Q. Liu, K. Harshman, S.V. Tavtigian, E. Stocken, R.S. Day, B.E. Johnson, M.H. Skolnick, A cell cycle regulator potentially involved in genesis of many tumor types, Science 264 (1994) 436-440.
97. [97] E.A. Holland, S.C. Beaton, T.M. Becker, O.M.C. Grulet, B.A. Peters, H. Rizos, R.F. Kefford, G.J. Mann, Analysis of the p16 gene, CDKN2, in 17 Australian melanoma kindreds, Oncogene 11 (1995) 2289-2294.
98. [98] P.M. Pollock, J.V. Pearson, N.K. Hayward, Compilation of somatic mutations of the CDNK2 gene in human cancers: non-random distribution of base substitutions, Genes Chromosomes Cancer 15 (1996) 77-88.
99. [99] D.E. Quelle, F. Zindy, R.A. Ashmun, C.J. Sherr, Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest, Cell 83 (1995) 993-1000.
100. [100] D.A. Haber, Splicing into senescence:the curious case of p16 and p19ARF, Cell 91 (1997) 555-558.
101. [101] M. Serrano, H.W. Lee, L. Chin, C. Cordon-Cardo, D. Beach, R.A. DePinho, Role of the INK4a locus in tumor suppression and cell mortality, Cell 85 (1996) 27-37.
102. [102] T. Kamijo, F. Zindy, M.F. Roussel, D.E. Quelle, J.R. Downing, R.A. Ashmun, G. Grosveld, C.J. Sherr, Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF, Cell 91 (1997) 649-659.
103. [103] J. Hall, M. Lee, B. Newman, J. Morrow, L. Anderson, B. Huey, M.C. King, Linkage of early-onset familial breast cancer to chromosome 17q21, Science 250 (1990) 1684-1689.
104. [104] R. Wooster, S. Neuhausen, J. Mangion, Y. Quirk, D. Ford, N. Collins, K. Nguyen, S. Seal, T. Tran, D. Averill, Localization of breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13, Science (1994) 2088-2090.
105. [105] R. Wooster, J. Bignell, Lancaster, S. Swift, S. Seal, J. Mangion, N. Collins, S. Gregory, C. Gumbs, G. Micklem, R. Barfoot, R. Hamoudi, S. Patel, C. Rice, P. Biggs, Y. Hashim, A. Smith, F. Connor, A. Arason, J. Gudmundson, D. Fice-Ponder, R. Eeles, J. Peto, P. Devilee, C. Cornelisse, H. Lynch, S. Narod, G. Lenoir, V. Egilsson, R.B. Barkadottir, D.F. Easton, D.R. Bentley, P.A. Futreal, A. Ashworth, M.R. Stratton, Identification of the breast cancer susceptibility gene BRCA2, Nature 378 (1995) 789-792.
106. [106] Y. Miki, J. Swensen, D. Shattuckeidens, P.A. Futreal, K. Harshman, S. Tavitigian, Q.Y. Liu, C. Cochran, W. Bennett, W. Ding, R. Bell, J. Rosenthal, C. Hussey, T. Tran, M. McClure, C. Frye, T. Hattier, R. Phelps, A. Haugenstrano, K. Katcher, K. Yakumo, Z. Gholami, D. Shaffer, S. Stone, S. Bayer, C. Wray, R. Bogden, P. Dayananth, J. Warda, P. Tonin, S. Narod, P.K. Bristow, F.H. Norris, L. Helvering, P. Morrison, P. Rosteck, M. Lai, J.C. Barrett, C. Lewis, S. Neuhausen, L. Canonalbright, D. Goldgar, R. Wiseman, A. Kamb, M.H. Skolnick, A strong candidate for the breast and ovarian-cancer susceptibility gene BRCA1, Science 266 (1994) 66-71.
107. [107] S. Tavitigian, J. Simard, J. Rommens, F. Couch, D. Sharluck-Eidens, S. Neuhausen, S. Marajver, S. Thorlacius, K. Offit, D. Stoppa-Lyonnet, The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds, Nat. Genet. 12 (1996) 333-337.
108. [108] L.H. Castilla, F.J. Cough, M.R. Erdos, K.F. Hoskins, K. Calzone, J.E. Garber, J. Boyd, M.B. Lubin, M.L. Deshano, L.C. Brody, Mutations in the BRCA1 gene families with early onset breast and ovarian cancer, Nat. Genet. 8 (1994) 387-391.
109. [109] L.S. Friedman, E.A. Ostermeyer, C.I. Szabo, P. Dowd, E.D. Lynch, S.E. Rowell, M.C. King, Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in 10 families, Nat. Genet. 8 (1994) 399-404.
110. [110] P.A. Futreal, Q. Liu, D. Sharluck-Eidens, C. Cochran, K. Harshman, S. Tavitigian, L.M. Bennett, A. Haugen-Strano, J. Swensen, Y. Miki, BRCA1 mutations in primary breast and ovarian carcinomas, Science 266 (1994) 120-122.
111. [111] J.V. Rajan, S.T. Marquis, H.P. Gardner, L.A. Chodosh, Development expression of BRCA2 colocalizes with BRCA1 and is associated with proliferation and differentiation in multiple tissues, Dev. Biol. 184 (1997) 385-401.
112. [112] Breast Cancer Linkage Consortium, D.F. Easton, D. Ford, D.T. Bishop, Breast and ovarian cancer incidence in BRCA1-mutation carriers, Am. J. Hum. Genet. 56 (1995) 265-271.
113. [113] S.A. Gayther, W. Warren, S. Mazoyer, P.A. Russell, P.A. Harrington, M. Chiano, S. Seal, R. Hamoudi, E.J. van Rensburg, A.M. Dunning, Germline mutations of the BRCA1 gene mutations in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation, Nat. Genet. 11 (1995) 428-433.
114. [114] M. Schutte, L.T. DaCosta, S.A. Hahn, C.A. Moskaluk, A.T.M.S. Hoque, E. Rozenblum, C.L. Weinstein, M. Bittner, P.S. Meltzer, J.M. Trent, Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 5950-5954.
115. [115] M.M. Goggins, M. Schutte, J.L. Lu, C.A. Moskaluk, C.L. Weinstein, G.M. Petersen, C.J. Yeo, C.E. Jackson, H.T. Lynch, R.H. Hruban, S.E. Kern, Germline BRCA2 mutations in patients with apparently sporadic pancreatic carcinomas, Cancer Res. 56 (1996) 5360-5364.
116. [116] D.H.F. Teng, R. Bogden, J. Mitchell, M. Baumgard, R. Bell, S. Berry, T. Davis, P.C. Ha, R. Kehrer, S. Jammulapati, Q. Chen, K. Offit, M.H. Skolnick, S. Tavitigian, S. Jhanwar, S. Swedlund, A.K. Wong, A. Kamb, Low incidence of BRCA2 mutations in breast carcinoma and other cancers, Nat. Genet. 13 (1996) 241-244.
117. [117] Lancaster, R. Wooster, J. Mangion, C.M. Phelan, C. Cochran, C. Gumbs, S. Seal, R. Barfoot, N. Collins, G. Bingell, BRCA2 mutations in primary breast and ovarian cancers, Nat. Genet. 13 (1996) 238-240.
118. [118] Y. Miki, T. Katagiri, F. Kasumi, T. Yoshimoto, Y. Nakamura, Mutation analysis in the BRCA2 gene in primary breast cancers, Nat. Genet. 13 (1996) 245-247.
119. [119] M.S. Chapman, I.M. Verma, Transcriptional activation by BRCA1, Nature 382 (1996) 678-679.
120. [120] A.N.A. Monteiro, A. August, H. Hanafusa, Evidence for a transcriptional activation function of BRCA1 C-terminal region, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 13595-13599.
121. [121] J. Milner, B. Ponder, L. Hughes-Davies, M. Seltmann, T. Kouzarides, Transcriptional activation functions in BRCA2, Nature 386 (1997) 772-773.
122. [122] K. Somasundaram, H. Zhang, Y. Zeng, Y. Houvras, Y. Peng, G.S. Wu, J.D. Licht, B.L. Weber, W.S. El-Deiry, Arrest of the cell cycle by the tumor-suppressor BRCA1 requires the CDK-inhibitor p21, Nature 389 (1997) 187-190.
123. [123] R. Scully, J. Chen, A. Plug, Y. Xiao, D. Weaver, J. Feunteum, T. Ashley, D.M. Livingston, Association of BRCA1 with Rad51 in mitotic and meiotic cells, Cell 88 (1997) 265-275.
124. [124] S.K. Sharan, M. Morimatsu, U. Albrecht, D.S. Lim, E. Regel, C. Dinh, A. Sands, G. Eichele, P. Hasty, A. Bradley, Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking BRCA2, Nature 386 (1997) 804-810.
125. [125] R. Hakem, J.L. de la Pompa, C. Sirard, R. Mo, M. Woo, A. Hakem, Reitmar, F. Billia, E. Firpo, C.C. Hui, J. Roberts, J. Rossant, T.W. Mak, The tumor suppressor gene BRCA1 is required for embryonic cellular proliferation in the mouse, Cell 85 (1996) 1009-1023.
126. [126] T. Ludwig, D.L. Chapman, V.E. Papaioannou, A. Efstratiadis, Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos, Genes Dev. 11 (1997) 1226-1241.
127. [127] C.Y. Liu, A. Flesken-Nikitin, S. Li, Y. Zeng, W.H. Lee, Inactivation of the mouse BRCA1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development, Genes Dev. 10 (1996) 1835-1843.
128. [128] L.C. Gowen, B.L. Johnson, A.M. Latour, K.K. Sulik, B. Koller, Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities, Nat. Genet. 12 (1996) 191-194.
129. [129] A. Suzuki, J. De la Pompa, R. Hakem, A. Elia, R. Yoshida, R. Mo, H. Nishina, T. Chuang, A. Wakeham, A. Itie, W. Koo, P. Billia, A. Ho, M. Fukumoto, C.C. Hui, T.W. Mak, Brca2 is required for embryonic cellular proliferation in the mouse, Genes Dev. 11 (1997) 1242-1252.
130. [130] F. Connor, A. Smith, R. Wooster, M. Stratton, A. Dixon, E. Canpbell, T.C. Tait, T. Freeman, A. Ashworth, Cloning, chromosomal mapping and expression pattern of the mouse Brca2 gene, Hum. Mol. Genet. 6 (1996) 291-300.
131. [131] J.V. Rajan, M. Wang, S.T. Marquis, L.A. Chodosh, Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 13078-13083.
132. [132] R. Hakem, J.L. de la Pompa, A. Elia, J. Potter, T.W. Mak, Partial rescue of Brca1 (5-6) early embryonic lethality by p53 or p21 null mutation, Nat. Genet. 16 (1997) 298-302.
133. [133] D.A. Haber, D.E. Housman, The genetics of Wilm's tumor, Adv. Cancer Res. 59 (1992) 41-68.
134. [134] M.J. Coppes, V. Huff, J. Pelletier, Venys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1, J. Pediatr. 12 (1993) 144-148.
135. [135] I.A. Drummond, S.L. Madden, N.P. Rohwer, G.I. Bell, V.P. Sukhatme, F.I. Rauscher, Repression of the insulin-like growth factor II gene by the Wilm's tumor suppressor gene, WT1, Science 257 (1992) 674-678.
136. [136] J.A. Kreidberg, H. Sariola, J.M. Loring, M. Maeda, J. Pelletier, D. Housman, R. Jaenisch, WT-1 is required for early kidney development, Cell 74 (1993) 679-691.
137. [137] J.R. Gnarra, D.R. Duan, Y. Weng, J.S. Humprey, D.Y. Chen, S. Lee, A. Pause, C.F. Dudley, F. Latif, I. Kuzmin, L. Schmidt, P.M. Duh, T. Stackhouse, F. Chen, T. Kishida, M.H. Wei, M.I. Lerman, Z. Abar, R.D. Klausner, W.M. Linehan, Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal cell carcinoma, Biochim. Biophys. Acta 1242 (1996) 201-210.
138. [138] B.R. Seizinger, G.A. Rouleau, L.J. Ozelius, A.H. Lane, G.E. Farmer, J.M. Lamiell, J. Haines, J.W. Yuen, Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma, Nature 332 (1988) 268-269.
139. [139] F. Latif, K. Tory, J.R. Gnarra, M. Yao, F.M. Duh, M.L. Orcutt, T. Stackhouse, I. Kuzmin, W. Modi, L. Geil et al., Identification of the von Hippel-Lindau disease tumor suppressor gene, Science 260 (1993) 1317-1320.
140. [140] D.R. Duan, J.S. Humprey, D.Y.T. Chen, R.D. Klausner, Characterization of the VHL tumor suppressor gene product:Localization,complex formation, and the effect of natural inactivating mutations, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6459-6463.
141. [141] T. Aso, W.S. Lane, J.W. Conaway, R.C. Conaway, Elongin (SIII): a multisubunit regulator of elongation by RNA polymerase II, Science 269 (1995) 1439-1443.
142. [142] A. Kibel, O. Iliopoulos, J.A. DeCaprio, W.G.J. Kaelin, Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C, Science 269 (1995) 1444-1446.
143. [143] J.R. Gnarra, J.M. Ward, F.D. Porter, J.R. Wagner, D.E. Devor, A. Grinberg, M. Emmert-Buck, H. Westphal, R.D. Klausner, W.M. Linehan, Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice, Proc. Natl. Acad. Sci. U.S.A. (1997) 9102-9107.
144. [144] E.C.R. Maandag, M. van der Valk, M. Vlaar, C. Feltkamp, J.M. O'Brien, M. van Roon, N. van der Lugt, A. Berns, H. te Riele, Developmental rescue of an embryonic lethal mutation in retinoblastoma gene in chimeric mice, EMBO J. 13 (1994) 4260-4268.
145. [145] M.H. Lee, B.O. Williams, G. Mulligan, S. Mukai, R.T. Bronson, N. Dyson, E. Harlow, T. Jacks, Targeted disruption of p107: functional overlap between p107 and Rb, Genes Dev. 10 (1996) 1621-1632.
146. [146] D. Cobrinik, M.H. Lee, G. Hannon, R.T. Bronson, N. Dyson, E. Harlow, D. Beach, R.A. Weinberg, T. Jacks, Shared role of the pRB-related p130 and p107 proteins in limb development, Genes Dev. 10 (1996) 1633-1644.
147. [147] C.A. Jost, M.C. Marin, W.G.J. Kaelin, p73 is a human p53-related protein that can induce apoptosis, Nature 389 (1997) 191-194.
148. [148] M. Kaghad, H. Bonnet, A. Yang, L. Creancier, J.C. Biscan, A. Valent, A. Minty, P. Chalon, J.M. Lelias, X. Dumont, P. Ferrara, F. McKeon, D. Caput, Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers, Cell 90 (1997) 809-819.
149. [149] K. Rajewsky, H. Gu, R. Kuhn, U.A. Betz, W. Muller, J. Roes, F. Schwenk, Conditional gene targeting, J. Clin. Invest. 98 (1996) 600-603.