Gastroenterology
Volume 136, Issue 3 , Pages 780-798 , March 2009

Mouse Models of Colon Cancer

  • Makoto Mark Taketo

      Affiliations

    • Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    • Corresponding Author InformationReprint requests Address requests for reprints to: Makoto Mark Taketo, MD, PhD, Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan or Winfried Edelmann, PhD, Department of Cell Biology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461
    • ,
  • Winfried Edelmann

      Affiliations

    • Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
    • Corresponding Author InformationReprint requests Address requests for reprints to: Makoto Mark Taketo, MD, PhD, Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan or Winfried Edelmann, PhD, Department of Cell Biology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461

Received 11 September 2008 ,Accepted 12 December 2008.

References 

  1. Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991;66:589–600
  2. Kinzler KW, Nilbert MC, Vogelstein B, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991;251:1366–1370
  3. Polakis P. The oncogenic activation of beta-catenin. Curr Opin Genet Dev. 1999;9:15–21
  4. Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC−/− colon carcinoma. Science. 1997;275:1784–1787
  5. Oshima H, Oshima M, Kobayashi M, et al. Morphological and molecular processes of polyp formation in ApcΔ716 knockout mice. Cancer Res. 1997;57:1644–1649
  6. Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science. 1990;247:322–324
  7. Su LK, Kinzler KW, Vogelstein B, et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992;256:668–670
  8. Fodde R, Edelmann W, Yang K, et al. A targeted chain-termination mutation in the mouse Apc gene results in multiple tumors. Proc Natl Acad Sci U S A. 1994;91:8969–8973
  9. Oshima M, Oshima H, Kitagawa K, et al. 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. 1995;92:4482–4486
  10. Aoki K, Tamai Y, Horiike S, et al. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Δ716 Cdx2+/− compound mutant mice. Nat Genet. 2003;35:323–330
  11. Munemitsu S, Souza B, Müller O, et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994;54:3676–3681
  12. Smith KJ, Levy DB, Maupin P, et al. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 1994;54:3672–3675
  13. Nathke IS, Adams CL, Polakis P, et al. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol. 1996;134:165–178
  14. Mimori-Kiyosue Y, Shiina N, Tsukita S. Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J Cell Biol. 2000;148:505–517
  15. Rosin-Arbesfeld R, Ihrke G, Bienz M. Actin-dependent membrane association of the APC tumor suppressor in polarized mammalian epithelial cells. EMBO J. 2001;20:5929–5939
  16. Kawasaki Y, Senda T, Ishidate T, et al. Asef, a link between the tumor suppressor APC and G-protein signaling. Science. 2000;289:1194–1197
  17. Kawasaki Y, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol. 2003;5:211–215
  18. Watanabe T, Wang S, Noritake J, et al. Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. Dev Cell. 2004;7:871–883
  19. Kawasaki Y, Sagara M, Shibata Y, et al. Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42. Oncogene. 2007;26:7620–7627
  20. Colnot S, Niwa-Kawakita M, Hamard G, et al. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Invest. 2004;84:1619–1630
  21. Coletta PL, Müller AM, Jones EA, et al. Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis. Blood. 2004;103:1050–1058
  22. Erdman SE, Sohn JJ, Rao VP, et al. CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res. 2005;65:3998–4004
  23. Benhamouche S, Decaens T, Godard C, et al. Apc tumor suppressor gene is the “zonation-keeper” of mouse. Dev Cell. 2006;10:759–770
  24. Baltgalvis KA, Berger FG, Pena MM, et al. Interleukin-6 and cachexia in ApcMin/+ mice. Am J Physiol Regul Integr Comp Physiol. 2008;294:R393–R401
  25. Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (Part I). J Natl Cancer Inst. 1998;90:1529–1536
  26. Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). J Natl Cancer Inst. 1998;90:1609–1620
  27. Chulada PC, Thompson MB, Mahler JF, et al. Genetic disruption of Ptgs-1, as well as of Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 2000;60:4705–4708
  28. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell. 1996;87:803–809
  29. Oshima M, Murai(Hata) N, Kargman S, et al. Chemoprevention of intestinal polyposis in the ApcΔ716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res. 2001;61:1733–1740
  30. Steinbach G, Lynch PM, Phillips RKS, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342:1946–1952
  31. Takeda H, Sonoshita M, Sugihara K, et al. Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Cancer Res. 2003;63:4872–4877
  32. Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk assessment with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–1080
  33. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352:1092–1102
  34. Sonoshita M, Takaku K, Sasaki N, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice. Nat Med. 2001;7:1048–1051
  35. Sheng H, Shao J, Washington MK, et al. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem. 2001;276:18075–18081
  36. Cherukuri DP, Chen XB, Goulet AC, et al. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res. 2007;313:2969–2979
  37. Yang L, Huang Y, Porta R, et al. Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 antagonism. Cancer Res. 2006;66:9665–9672
  38. de Leng WW, Westerman AM, de Rooij FW, et al. Cyclooxygenase 2 expression and molecular alterations in Peutz-Jeghers hamartomas and carcinomas. Clin Cancer Res. 2003;9:3065–3072
  39. Takeda H, Miyoshi H, Tamai Y, et al. Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas. Br J Cancer. 2004;90:701–704
  40. DuBois RN. New agents for cancer prevention. J Natl Cancer Inst. 2002;94:1732–1733
  41. Castellone MD, Teramoto H, Williams BO, et al. Prostaglandin E2 promotes coon cancer cell growth through a novel Gs-axin-b-catenin signaling axis. Science. 2005;310:1504–1510
  42. Rao CV, Yang YM, Swamy MV, et al. Colonic tumorigenesis in BubR1+/−ApcMin/+ compound mutant mice is linked to premature separation of sister chromatids and enhanced genomic instability. Proc Natl Acad Sci U S A. 2005;102:4365–4370
  43. Oshima M, Takahashi M, Oshima H, et al. Effects of docosahexaenoic acid (DHA) on intestinal polyp development in ApcΔ716 knockout mice. Carcinogenesis. 1995;16:2605–2607
  44. Hioki K, Shivapurkar N, Oshima H, et al. Suppression of intestinal polyp development by low-fat and high-fiber diet in ApcΔ716 knockout mice. Carcinogenesis. 1997;18:1863–1865
  45. Yang K, Edelman W, Fan K, et al. Dietary modulation of carcinoma development in a mouse model for human familial adenomatous polyposis. Cancer Res. 1998;58:5713–5717
  46. Mai V, Colbert LH, Berrigan D, et al. Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in ApcMin mice through different mechanisms. Cancer Res. 2003;63:1752–1755
  47. Mehl KA, Davis JM, Clements JM, et al. Decreased intestinal polyp multiplicity is related to excercise mode and gender in ApcMin/+ mice. J Appl Physiol. 2005;98:2219–2225
  48. Fenton JI, Hord NG. Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research. Carcinogenesis. 2006;27:893–902
  49. Romagnolo B, Berrebi D, Saadi-Keddoucci S, et al. Intestinal dysplasia and adenoma in transgenic mice after overexpression of an activated β-catenin. Cancer Res. 1999;59:3875–3879
  50. Harada N, Tamai Y, Ishikawa T, et al. Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene. EMBO J. 1999;18:5931–5942
  51. Gounari F, Signoretti S, Bronson R, et al. Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene. 2002;21:4099–4107
  52. Lickert H, Domon C, Huls G, et al. Wnt/β-catenin signaling regulates the expression of the homeobox gene Cdx1 in embryonic intestine. Development. 2000;127:3805–3813
  53. Gounaris F, Aifantis I, Khazaie K, et al. Somatic activation of β-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development. Nat Immunol. 2001;2:863–869
  54. Taketo MM. Wnt signaling and gastrointestinal tumorigenesis in mouse models. Oncogene. 2006;25:7522–7530
  55. Takaku K, Oshima M, Miyoshi H, et al. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell. 1998;92:645–656
  56. Munoz NM, Upton M, Rojas A, et al. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res. 2006;66:9837–9844
  57. Kitamura T, Kometani K, Hashida H, et al. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat Genet. 2007;39:467–475
  58. Kitamura T, Taketo MM. Keeping out the bad guys: gateway to cellular target therapy. Cancer Res. 2007;67:10099–10102
  59. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387–2392
  60. Gounaris E, Erdman SE, Restaino C, et al. Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci U S A. 2007;104:19977–19982
  61. Shao J, Washington K, Saxena R, et al. Heterozygous disruption of the PTEN promotes intestinal neoplasia in APCmin/+ mouse: roles of osteopoitin. Carcinogenesis. 2007;28:2476–2483
  62. Petrova TV, Nykänen A, Norrimén C, et al. Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. Cancer Cell. 2008;13:407–419
  63. Lynch HT, Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome) (An updated review). Cancer. 1996;78:1149–1167
  64. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003;21:1174–1179
  65. Vasen HF, Boland CR. Progress in genetic testing, classification, and identification of Lynch syndrome. JAMA. 2005;293:2028–2030
  66. Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007;21:2525–2538
  67. Vasen HF, Mecklin JP, Khan PM, et al. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34:424–425
  68. Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453–1456
  69. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science. 1993;260:812–816
  70. Ionov Y, Peinado MA, Malkhosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–5561
  71. Umar A. Lynch syndrome (HNPCC) and microsatellite instability. Dis Markers. 2004;20:179–180
  72. Iyer RR, Pluciennik A, Burdett V, et al. DNA mismatch repair: functions and mechanisms. Chem Rev. 2006;106:302–323
  73. Kolodner RD, Marsischky GT. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev. 1999;9:89–96
  74. Edelmann W, Umar A, Yang K, et al. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res. 2000;60:803–807
  75. Genschel J, Littman SJ, Drummond JT, et al. Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha. J Biol Chem. 1998;273:19895–19901
  76. Marsischky GT, Filosi N, Kane MF, et al. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996;10:407–420
  77. Umar A, Risinger JI, Glaab WE, et al. Functional overlap in mismatch repair by human MSH3 and MSH6. Genetics. 1998;148:1637–1646
  78. de Vries SS, Baart EB, Dekker M, et al. Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis. Genes Dev. 1999;13:523–531
  79. Edelmann W, Cohen PE, Kneitz B, et al. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet. 1999;21:123–127
  80. Kneitz B, Cohen PE, Avdievich E, et al. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev. 2000;14:1085–1097
  81. Buermeyer AB, Deschênes SM, Baker SM, et al. Mammalian mismatch repair. Annu Rev Genet. 1999;33:533–564
  82. Blackwell LJ, Martik D, Bjornson KP, et al. Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism. J Biol Chem. 1998;273:32055–32062
  83. Fishel R. Mismatch repair, molecular switches, and signal transduction. Genes Dev. 1998;12:2096–2101
  84. Junop MS, Obmolova G, Rausch K, et al. Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair. Mol Cell. 2001;7:1–12
  85. Sacho EJ, Kadyrov FA, Modrich P, et al. Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha. Mol Cell. 2008;29:112–121
  86. Fang WH, Modrich P. Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction. J Biol Chem. 1993;268:11838–11844
  87. Wang H, Hays JB. Mismatch repair in human nuclear extracts (Time courses and ATP requirements for kinetically distinguishable steps leading to tightly controlled 5′ to 3′ and aphidicolin-sensitive 3′ to 5′ mispair-provoked excision). J Biol Chem. 2002;277:26143–26148
  88. Genschel J, Modrich P. Mechanism of 5′-directed excision in human mismatch repair. Mol Cell. 2003;12:1077–1086
  89. Constantin N, Dzantiev L, Kadyrov FA, et al. Human mismatch repair: reconstitution of a nick-directed bidirectional reaction. J Biol Chem. 2005;280:39752–39761
  90. Zhang Y, Yuan F, Presnell SR, et al. Reconstitution of 5′-directed human mismatch repair in a purified system. Cell. 2005;122:693–705
  91. Kadyrov FA, Dzantiev L, Constantin N, et al. Endonucleolytic function of MutLalpha in human mismatch repair. Cell. 2006;126:297–308
  92. Wei K, Clark AB, Wong E, et al. Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Genes Dev. 2003;17:603–614
  93. Fishel R. The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Res. 2001;61:7369–7374
  94. Stojic L, Brun R, Jiricny J. Mismatch repair and DNA damage signalling. DNA Repair (Amst). 2004;3:1091–1101
  95. Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008;18:85–98
  96. Karran P. Mechanisms of tolerance to DNA damaging therapeutic drugs. Carcinogenesis. 2001;22:1931–1937
  97. Kat A, Thilly WG, Fang WH, et al. An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc Natl Acad Sci U S A. 1993;90:6424–6428
  98. Stojic L, Mojas N, Cejka P, et al. Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase. Genes Dev. 2004;18:1331–1344
  99. Adamson AW, Beardsley DI, Kim WJ, et al. Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2. Mol Biol Cell. 2005;16:1513–1526
  100. Caporali S, Falcinelli S, Starace G, et al. DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol Pharmacol. 2004;66:478–491
  101. Yan T, Desai AB, Jacobberger JW, et al. CHK1 and CHK2 are differentially involved in mismatch repair-mediated 6-thioguanine-induced cell cycle checkpoint responses. Mol Cancer Ther. 2004;3:1147–1157
  102. Yoshioka K, Yoshioka Y, Hsieh P. ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell. 2006;22:501–510
  103. Peled JU, Kuang FL, Iglesias-Ussel MD, et al. The biochemistry of somatic hypermutation. Annu Rev Immunol. 2008;26:481–511
  104. Kolas NK, Cohen PE. Novel and diverse functions of the DNA mismatch repair family in mammalian meiosis and recombination. Cytogenet Genome Res. 2004;107:216–231
  105. McMurray CT. Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease. DNA Repair (Amst). 2008;7:1121–1134
  106. Edelmann L, Edelmann W. Loss of DNA mismatch repair function and cancer predisposition in the mouse: animal models for human hereditary nonpolyposis colorectal cancer. Am J Med Genet C Semin Med Genet. 2004;129C:91–99
  107. Felton KE, Gilchrist DM, Andrew SE. Constitutive deficiency in DNA mismatch repair. Clin Genet. 2007;71:483–498
  108. de Wind N, Dekker M, Berns A, et al. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995;82:321–330
  109. Reitmair AH, Redston M, Cai JC, et al. Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice. Cancer Res. 1996;56:3842–3849
  110. Smits R, Hofland N, Edelmann W, et al. Somatic apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activity. Genes Chromosomes Cancer. 2000;29:229–239
  111. de Wind N, Dekker M, van Rossum A, et al. Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res. 1998;58:248–255
  112. Hinoi T, Akyol A, Theisen BK, et al. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res. 2007;67:9721–9730
  113. Edelmann W, Yang K, Umar A, et al. Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell. 1997;91:467–477
  114. Kolodner RD, Tytell JD, Schmeits JL, et al. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999;59:5068–5074
  115. de Wind N, Dekker M, Claij N, et al. HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. Nat Genet. 1999;23:359–362
  116. Wijnen J, de Leeuw W, Vasen H, et al. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet. 1999;23:142–144
  117. Baker SM, Plug AW, Prolla TA, et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996;13:336–342
  118. Edelmann W, Cohen PE, Kane M, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell. 1996;85:1125–1134
  119. Prolla TA, Baker SM, Harris AC, et al. Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet. 1998;18:276–279
  120. Edelmann W, Yang K, Kuraguchi M, et al. Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res. 1999;59:1301–1307
  121. Baker SM, Bronner CE, Zhang I, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995;82:309–320
  122. Senter L, Clendenning M, Sotamaa K, et al. The clinical phenotype of Lynch syndrome because of germ-line PMS2 mutations. Gastroenterology. 2008;135:419–428
  123. Miller AJ, Dudley SD, Tsao JL, et al. Tractable Cre-lox system for stochastic alteration of genes in mice. Nat Methods. 2008;5:227–229
  124. Chen PC, Dudley S, Hagen W, et al. Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer Res. 2005;65:8662–8670
  125. Wu Y, Berends MJ, Post JG, et al. Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms. Gastroenterology. 2001;120:1580–1587
  126. Kucherlapati M, Nguyen A, Kuraguchi M, et al. Tumor progression in Apc(1638N) mice with Exo1 and Fen1 deficiencies. Oncogene. 2007;26:6297–6306
  127. Reitmair AH, Cai JC, Bjerknes M, et al. MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis. Cancer Res. 1996;56:2922–2926
  128. Baker SM, Harris AC, Tsao JL, et al. Enhanced intestinal adenomatous polyp formation in Pms2−/−; Min mice. Cancer Res. 1998;58:1087–1089
  129. Kuraguchi M, Yang K, Wong E, et al. The distinct spectra of tumor-associated Apc mutations in mismatch repair deficient Apc1638N mice define the roles of MSH3 and MSH6 in DNA repair and intestinal tumorigenesis. Cancer Res. 2001;61:7934–7942
  130. Toft NJ, Curtis LJ, Sansom OJ, et al. Heterozygosity for p53 promotes microsatellite instability and tumorigenesis on a Msh2 deficient background. Oncogene. 2002;21:6299–6306
  131. Young LC, Keuling AM, Lai R, et al. The associated contributions of p53 and the DNA mismatch repair protein Msh6 to spontaneous tumorigenesis. Carcinogenesis. 2007;28:2131–2138
  132. Kawate H, Sakumi K, Tsuzuki T, et al. Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes. Proc Natl Acad Sci U S A. 1998;95:5116–5120
  133. Qin X, Liu L, Gerson SL. Mice defective in the DNA mismatch gene PMS2 are hypersensitive to MNU induced thymic lymphoma and are partially protected by transgenic expression of human MGMT. Oncogene. 1999;18:4394–4400
  134. Colussi C, Fiumicino S, Giuliani A, et al. 1,2-Dimethylhydrazine-induced colon carcinoma and lymphoma in msh2(−/−) mice. J Natl Cancer Inst. 2001;93:1534–1540
  135. Toft NJ, Winton DJ, Kelly J, et al. Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine. Proc Natl Acad Sci U S A. 1999;96:3911–3915
  136. Wu TH, Marinus MG. Dominant negative mutator mutations in the mutS gene of Escherichia coli. J Bacteriol. 1994;176:5393–5400
  137. Drotschmann K, Clark AB, Tran HT, et al. Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene. Proc Natl Acad Sci U S A. 1999;96:2970–2975
  138. Peltomaki P, Vasen H. Mutations associated with HNPCC predisposition—update of ICG-HNPCC/INSiGHT mutation database. Dis Markers. 2004;20:269–276
  139. Lin DP, Wang Y, Scherer SJ, et al. An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Res. 2004;64:517–522
  140. Hess MT, Gupta RD, Kolodner RD. Dominant Saccharomyces cerevisiae msh6 mutations cause increased mispair binding and decreased dissociation from mispairs by Msh2-Msh6 in the presence of ATP. J Biol Chem. 2002;277:25545–25553
  141. Hess MT, Mendillo ML, Mazur DJ, et al. Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6 gene. Proc Natl Acad Sci U S A. 2006;103:558–563
  142. Yang G, Scherer SJ, Shell SS, et al. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell. 2004;6:139–150
  143. Berends MJ, Wu Y, Sijmons RH, et al. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet. 2002;70:26–37
  144. Avdievich E, Reiss C, Scherer SJ, et al. Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis. Proc Natl Acad Sci U S A. 2008;105:4247–4252
  145. Burstein E, Fearon ER. Colitis and cancer: a tale of inflammatory cells and their cytokines. J Clin Invest. 2008;118:464–467
  146. Sadlack B, Merz H, Schorle H, et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993;75:253–261
  147. Kuhn R, Lohler J, Rennick D, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–274
  148. Berg DJ, Davidson N, Kuhn R, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996;98:1010–1020
  149. Simpson SJ, Mizoguchi E, Allen D, et al. Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis. Eur J Immunol. 1995;25:2618–2625
  150. Shah SA, Simpson SJ, Brown LF, et al. Development of colonic adenocarcinomas in a mouse model of ulcerative colitis. Inflamm Bowel Dis. 1998;4:196–202
  151. Schultz M, Tonkonogy SL, Sellon RK, et al. IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation. Am J Physiol. 1999;276:G1461–G1472
  152. Sellon RK, Tonkonogy S, Schultz M, et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998;66:5224–5231
  153. Kado S, Uchida K, Funabashi H, et al. Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. Cancer Res. 2001;61:2395–2398
  154. Engle SJ, Ormsby I, Pawlowski S, et al. Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res. 2002;62:6362–6366
  155. Chu FF, Esworthy RS, Chu PG, et al. Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res. 2004;64:962–968
  156. Van der Sluis M, De Koning BA, De Bruijn AC, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology. 2006;131:117–129
  157. Velcich A, Yang W, Heyer J, et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science. 2002;295:1726–1729
  158. Rudolph U, Finegold MJ, Rich SS, et al. Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet. 1995;10:143–150
  159. Kohonen-Corish MR, Daniel JJ, te Riele H, et al. Susceptibility of Msh2-deficient mice to inflammation-associated colorectal tumors. Cancer Res. 2002;62:2092–2097
  160. Greten FR, Eckmann L, Greten TF, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–296
  161. Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731–734
  162. Maeda S, Hsu LC, Liu H, et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005;307:734–738
  163. Fukata M, Chen A, Vamadevan AS, et al. Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology. 2007;133:1869–1881
  164. Popivanova BK, Kitamura K, Wu Y, et al. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest. 2008;118:560–570
  165. Zhu Y, Richardson JA, Parada LF, et al. Smad3 mutant mice develop metastatic colorectal cancer. Cell. 1998;94:703–714
  166. Yang X, Letterio JJ, Lechleider RJ, et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-b. EMBO J. 1999;18:1280–1291
  167. Datto MB, Frederick JP, Pan L, et al. Targeted disruption of Smad3 reveals an essential role in transforming growth factorβ-mediated signal transduction. Mol Cell Biol. 1999;19:2495–2504
  168. Maggio-Price L, Treuting P, Zeng W, et al. Helicobacter infection is required for inflammation and colon cancer in Smad3-deficient mice. Cancer Res. 2006;66:828–838
  169. Bohr UR, Selgrad M, Ochmann C, et al. Prevalence and spread of enterohepatic Helicobacter species in mice reared in a specific-pathogen-free animal facility. J Clin Microbiol. 2006;44:738–742
  170. Kobaek-Larsen M, Thorup I, Diederichsen A, et al. Review of colorectal cancer and its metastasis in rodent models: comparative aspects with those in humans. Comp Med. 2000;50:16–26
  171. Heijstek MW, Kranenburg O, Borel Rinkes IHM. Mouse models of colorectal cancer and liver metastasis. Dig Surg. 2005;22:16–25
  172. Alencar H, King R, Fiunovics M, et al. A novel mouse model for segmental orthotopic colon cancer. Int J Cancer. 2005;117:335–339
  173. Céspedes MV, Espina C, Garcia-Cabezas MA, et al. Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol. 2007;170:1077–1085
  174. Tsutsumi S, Kuwano H, Morinaga N, et al. Animal model of para-aortic lymph node metastasis. Cancer Lett. 2001;169:77–85
  175. Sun FX, Sasson AR, Jiang P, et al. An ultra-metastatic model of human colon cancer in nude mice. Clin Exp Metastasis. 1999;17:41–48
  176. Thalheimer A, Illert B, Beuter M, et al. Feasibility and limits of an orthotopic human colon cancer model in nude mice. Comp Med. 2006;56:105–109
  177. Corbett TH, Griswold DP, Roberts BJ, et al. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975;35:2434–2439
  178. Franks LM, Hemmings VJ. A cell line from an induced carcinoma of mouse rectum. J Pathol. 1978;124:35–38
  179. Takaku K, Sonoshita M, Sasaki N, et al. Suppression of intestinal polyposis in ApcΔ716 knockout mice by an additional mutation in the cytosolic phospholipase A2 gene. J Biol Chem. 2000;275:34013–34016
  180. Nakanishi M, Montrose DC, Clark P, et al. Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res. 2008;68:3251–3259
  181. Park JM, Kanaoka Y, Eguchi N, et al. Hematopoietic prostaglandin H synthase suppresses intestinal adenomas in ApcMin mice. Cancer Res. 2007;67:881–889
  182. 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;11:1913–1920
  183. Heppner Goss K, Risinger MA, Kordich JJ, et al. Enhanced tumor formation in mice heterozygous for Blm mutation. Science. 2002;297:2051–2053
  184. Rudolph KL, Millard M, Bosenberg MW, et al. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet. 2001;28:155–159
  185. Yang WC, Mathew J, Velcich A, et al. Targeted inactivation of the p21WAF/cip1 gene enhances Apc-initiated tumor formation and the tumor-promoting activity of a western-style high-risk diet by altering cell maturation in the intestinal mucosa. Cancer Res. 2001;61:565–569
  186. Philipp-Staheli J, Kim K-H, Payne SR, et al. Pathway-specific tumor suppression: reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice. Cancer Cell. 2002;1:355–368
  187. Wilson CL, Heppner KJ, Labovsky PA, et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A. 1997;94:1402–1407
  188. Yang W, Bancroft L, Liang J, et al. p27kip1 in intestinal tumorigenesis and chemoprevention in the mouse. Cancer Res. 2005;65:9363–9368
  189. Ahn B, Oshima H. Suppression of intestinal polyposis in (ApcMin/+) mice by inhibiting nitric oxide production. Cancer Res. 2001;61:8357–8360
  190. Laird PW, Jackson-Grusby L, Faseli A, et al. Suppression of intestinal neoplasia by DNA hypomethylation. Cell. 1995;81:197–205
  191. Sansom WJ, Berger J, Bishop SM, et al. Deficiency of Mbd2 suppresses intestinal tumorigenesis. Nat Genet. 2003;34:145–147
  192. Wong E, Yang K, Kuraguchi M, et al. Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation. Proc Natl Acad Sci U S A. 2002;99:14937–14942
  193. Millar CB, Guy J, Sansom OJ, et al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science. 2002;297:403–405
  194. Yamada T, Mori Y, Hayashi R, et al. Suppression of intestinal polyposis in Mdr1-deficient ApcMin/+ mice. Cancer Res. 2003;63:895–901
  195. Schaetzlein S, Kodandaramireddy NR, Ju Z, et al. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell. 2007;130:863–877
  196. Shibata H, Toyama K, Shioya H, et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science. 1997;278:120–123

 Conflicts of interest The authors disclose no conflicts.

 Funding The research programs in the Edelmann laboratory were supported by National Institutes of Health grants CA76329, CA93484, CA84301, and CA13330, and the research programs in the Taketo laboratory were supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan; Organization for Pharmaceutical Safety and Research, Japan; University of Tokyo–Banyu Pharmaceutical Co Joint Fund; Takeda Foundation; Mitsubishi Foundation; Sagawa Cancer Research Foundation; and a Littlefield-AACR Colon Cancer Metastasis Research Grant.

PII: S0016-5085(08)02307-X

doi: 10.1053/j.gastro.2008.12.049

Gastroenterology
Volume 136, Issue 3 , Pages 780-798 , March 2009

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