Skip to main content
SpringerLink
Log in

Conditional Mouse Models of Cancer

  • Chapter
Conditional Mutagenesis: An Approach to Disease Models

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 178))

Abstract

The development of inducible and conditional technologies allowed us to generate transgenic mouse models that faithfully recapitulate human tumorigenesis. It is possible to control, in time and space, the development of tumors in almost every mouse tissue. The result is that now we have available mouse models for all major human cancers. Novel noninvasive approaches to tumor imaging will enable us to follow tumor development and metastasis in vivo, as well as the effects of candidate therapeutic drugs. Such new generation tumor models, which accurately emulate the disease state in situ, should provide a useful platform with which to experimentally test drugs targeted to specific gene products, or combinations of genes that control rate-limiting steps of tumor development. In this review, we focus on the different mouse models for colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL (1985) The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318:533–538

    Article  PubMed  CAS  Google Scholar 

  • Ahn B, Ohshima H (2001) Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production. Cancer Res 61:8357–8360

    PubMed  CAS  Google Scholar 

  • Arango D, Corner GA, Wadler S, Catalano PJ, Augenlicht LH (2001) c-myc/p53 interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo. Cancer Res 61:4910–4915

    PubMed  CAS  Google Scholar 

  • Balmain A, Nagase H (1998) Cancer resistance genes in mice: models for the study of tumour modifiers. Trends Genet 14:139–144

    Article  PubMed  CAS  Google Scholar 

  • Behrens A, Sibilia M, David JP, Mohle-Steinlein U, Tronche F, Schutz G, Wagner EF (2002) Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver. EMBO J 21:1782–90

    Article  PubMed  CAS  Google Scholar 

  • Bruce WR (2003) Counter point: from animal models to prevention of colon cancer. Criteria for proceeding from preclinical studies and choice of models for prevention studies. Cancer Epidemiol Biomarkers Prev 12:401–404

    PubMed  Google Scholar 

  • Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  PubMed  CAS  Google Scholar 

  • Chin L, DePinho RA (2000) Flipping the oncogene switch: illumination of tumor maintenance and regression. Trends Genet 16:147–150

    Article  PubMed  CAS  Google Scholar 

  • Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O’Hagan R, Pantginis J, Zhou H, Horner JW 2nd, Cordon-Cardo C, Yancopoulos GD, DePinho RA (1999) Essential role for oncogenic Ras in tumour maintenance. Nature 400:468–472

    Article  PubMed  CAS  Google Scholar 

  • Chishima T, Miyagi Y, Wang X, Yamaoka H, Shimada H, Moossa AR, Hoffman RM (1997) Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression. Cancer Res 57:2042–2047

    PubMed  CAS  Google Scholar 

  • Clevers H (2004) Wnt breakers in colon cancer. Cancer Cell 5:5–6

    Article  PubMed  CAS  Google Scholar 

  • Colnot S, Niwa-Kawakita M, Hamard G, Godard C, Le Plenier S, Houbron C, Romagnolo B, Berrebi D, Giovannini M, Perret C (2004) Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Invest 84:1619–1630

    Article  PubMed  CAS  Google Scholar 

  • Corpet DE, Pierre F (2003) Point: from animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system. Cancer Epidemiol Biomarkers Prev 12:391–400

    PubMed  Google Scholar 

  • Corpet DE, Pierre F (2005) How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men. Eur J Cancer 41:1911–1922

    Article  PubMed  CAS  Google Scholar 

  • de Wind N, Dekker M, Berns A, Radman M, te Riele H (1995) Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82:321–330

    Article  PubMed  Google Scholar 

  • de Wind N, Dekker M, van Rossum A, van der Valk M, te Riele H (1998) Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res 58:248–255

    PubMed  Google Scholar 

  • Edelmann W, Yang K, Kuraguchi M, Heyer J, Lia M, Kneitz B, Fan K, Brown AM, Lipkin M, Kucherlapati R (1999) Tumorigenesis in Mlh1 and Mlh1/Apc1638 N mutant mice. Cancer Res 59:1301–1307

    PubMed  CAS  Google Scholar 

  • el Marjou F, Janssen KP, Chang BH, Li M, Hindie V, Chan L, Louvard D, Chambon P, Metzger D, Robine S (2004) Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39:186–193

    Article  PubMed  Google Scholar 

  • Felsher DW (2003) Cancer revoked: oncogenes as therapeutic targets. Nat Rev Cancer 3:375–380

    Article  PubMed  CAS  Google Scholar 

  • Felsher DW, Bishop JM (1999) Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4:199–207

    Article  PubMed  CAS  Google Scholar 

  • Fisher GH, Wellen SL, Klimstra D, Lenczowski JM, Tichelaar JW, Lizak MJ, Whitsett JA, Koretsky A, Varmus HE (2001) Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev 15:3249–3262

    Article  PubMed  CAS  Google Scholar 

  • Fodde R, Edelmann W, Yang K, van Leeuwen C, Carlson C, Renault B, Breukel C, Alt E, Lipkin M, Khan PM et al (1994) A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci U S A 91:8969–8973

    Article  PubMed  CAS  Google Scholar 

  • Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H (2001) Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 3:433–438

    Article  PubMed  CAS  Google Scholar 

  • Giuriato S, Felsher DW (2003) How cancers escape their oncogene habit. Cell Cycle 2:329–332

    PubMed  CAS  Google Scholar 

  • Guerra C, Mijimolle N, Dhawahir A, Dubus P, Barradas M, Serrano M, Campuzano V, Barbacid M (2003) Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell 4:111–120

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  • Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, Taketo MM (1999) Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J 18:5931–5942

    Article  PubMed  CAS  Google Scholar 

  • Harada N, Miyoshi H, Murai N, Oshima H, Tamai Y, Oshima M, Taketo MM (2002) Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res 62:1971–1977

    PubMed  CAS  Google Scholar 

  • Harrison DJ, Hooper ML, Armstrong JF, Clarke AR (1995) Effects of heterozygosity for the Rb-1t19neo allele in the mouse. Oncogene 10:1615–1620

    PubMed  CAS  Google Scholar 

  • Hoffman RM (1998) Orthotopic transplant mouse models with green fluorescent protein-expressing cancer cells to visualize metastasis and angiogenesis. Cancer Metastasis Rev 17:271–277

    Article  PubMed  Google Scholar 

  • Holland EC, Varmus HE (1998) Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice. Proc Natl Acad Sci U S A 95:1218–1223

    Article  PubMed  CAS  Google Scholar 

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359:295–300

    Article  PubMed  CAS  Google Scholar 

  • Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA (2001) Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15:3243–3248

    Article  PubMed  CAS  Google Scholar 

  • Jacoby RF, Seibert K, Cole CE, Kelloff G, Lubet RA (2000) The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 60:5040–5044

    PubMed  CAS  Google Scholar 

  • Janssen KP, el-Marjou F, Pinto D, Sastre X, Rouillard D, Fouquet C, Soussi T, Louvard D, Robine S (2002) Targeted expression of oncogenic K-ras in intestinal epithelium causes spontaneous tumorigenesis in mice. Gastroenterology 123:492–504

    Article  PubMed  CAS  Google Scholar 

  • Janssen KP, Abal M, El Marjou F, Louvard D, Robine S (2005) Mouse models of K-ras-initiated carcinogenesis. Biochim Biophys Acta 1765:145–154

    Google Scholar 

  • Janssen KP, Alberici P, Fsihi H, Gaspar C, Breukel C, Franken P, Rosty C, Abal M, El Marjou F, Smits R, Louvard D, Fodde R, Robine S (2006). APC and oncogenic KRAS are Synergistic in Enhancing Wnt Signaling in Intestinal Tumor Formation and Progression. Gastroenterology, 2006 (in press)

    Google Scholar 

  • Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, Jacks T (2001) Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 410:1111–1116

    Article  PubMed  CAS  Google Scholar 

  • Jonkers J, Berns A (2002) Conditional mouse models of sporadic cancer. Nat Rev Cancer 2:251–265

    Article  PubMed  CAS  Google Scholar 

  • Karlsson A, Giuriato S, Tang F, Fung-Weier J, Levan G, Felsher DW (2003) Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations. Blood 101:2797–2803

    Article  PubMed  CAS  Google Scholar 

  • Kuraguchi M, Edelmann W, Yang K, Lipkin M, Kucherlapati R, Brown AM (2000) Tumorassociated Apc mutations in Mlh1-/-Apc1638N mice reveal a mutational signature of Mlh1 deficiency. Oncogene 19:5755–5763

    Article  PubMed  CAS  Google Scholar 

  • Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, Li E, Weinberg RA, Jaenisch R (1995) Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81:197–205

    Article  PubMed  CAS  Google Scholar 

  • Lewis JS, Achilefu S, Garbow JR, Laforest R, Welch MJ (2002) Small animal imaging. Current technology and perspectives for oncological imaging. Eur J Cancer 38:2173–2188

    Article  PubMed  Google Scholar 

  • Luongo C, Moser AR, Gledhill S, Dove WF (1994) Loss of Apc+ in intestinal adenomas from Min mice. Cancer Res 54:5947–5952

    PubMed  CAS  Google Scholar 

  • Macleod KF, Jacks T (1999) Insights into cancer from transgenic mouse models. J Pathol 187:43–60

    Article  PubMed  CAS  Google Scholar 

  • MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buchberg AM (1995) The secretory phospholipase A2 gene is a candidate for the Mom1 locus, amajor modifier of ApcMin-induced intestinal neoplasia. Cell 81:957–966

    Article  PubMed  CAS  Google Scholar 

  • Meuwissen R, Jonkers J, Berns A (2001) Mouse models for sporadic cancer. Exp Cell Res 264:100–110

    Article  PubMed  CAS  Google Scholar 

  • Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, Innocent N, Cardiff RD, Schnall MD, Chodosh LA (2002) Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2:451–461

    Article  PubMed  CAS  Google Scholar 

  • Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247:322–324

    Article  PubMed  CAS  Google Scholar 

  • Moser AR, Dove WF, Roth KA, Gordon JI (1992) The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J Cell Biol 116:1517–1526

    Article  PubMed  CAS  Google Scholar 

  • Nateri AS, Spencer-Dene B, Behrens A (2005) Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature 437:281–285

    Article  PubMed  CAS  Google Scholar 

  • Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002–5011

    PubMed  CAS  Google Scholar 

  • Orner GA, Dashwood WM, Blum CA, Diaz GD, Li Q, Al-Fageeh M, Tebbutt N, Heath JK, Ernst M, Dashwood RH (2002) Response of Apc(min) and A33 (delta N beta-cat) mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Mutat Res 506–507:121–127

    PubMed  Google Scholar 

  • Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M (1995) 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 92:4482–4486

    Article  PubMed  CAS  Google Scholar 

  • Pelengaris S, Littlewood T, Khan M, Elia G, Evan G (1999) Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol Cell 3:565–577

    Article  PubMed  CAS  Google Scholar 

  • Pelengaris S, Khan M, Evan G (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2:764–776

    Article  PubMed  CAS  Google Scholar 

  • Prolla TA, Baker SM, Harris AC, Tsao JL, Yao X, Bronner CE, Zheng B, Gordon M, Reneker J, Arnheim N, Shibata D, Bradley A, Liskay RM (1998) Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet 18:276–279

    Article  PubMed  CAS  Google Scholar 

  • Reitmair AH, Redston M, Cai JC, Chuang TC, Bjerknes M, Cheng H, Hay K, Gallinger S, Bapat B, Mak TW (1996) Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice. Cancer Res 56:3842–3849

    PubMed  CAS  Google Scholar 

  • Saam JR, Gordon JI (1999) Inducible gene knockouts in the small intestinal and colonic epithelium. J Biol Chem 274:38071–3882

    Article  PubMed  CAS  Google Scholar 

  • Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, Matsumoto H, Takano H, Akiyama T, Toyoshima K, Kanamaru R, Kanegae Y, Saito I, Nakamura Y, Shiba K, Noda T (1997) Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278:120–123

    Article  PubMed  CAS  Google Scholar 

  • Shoemaker AR, Gould KA, Luongo C, Moser AR, Dove WF (1997) Studies of neoplasia in the Min mouse. Biochim Biophys Acta 1332: F25–F48

    PubMed  CAS  Google Scholar 

  • Shoemaker AR, Haigis KM, Baker SM, Dudley S, Liskay RM, Dove WF (2000) Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice. Oncogene 19:2774–2779

    Article  PubMed  CAS  Google Scholar 

  • Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P (1987) Coexpression of MM TV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49:465–475

    Article  PubMed  CAS  Google Scholar 

  • Smits R, Ruiz P, Diaz-Cano S, Luz A, Jagmohan-Changur S, Breukel C, Birchmeier C, Birchmeier W, Fodde R (2000) E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in mice. Gastroenterology 119:1045–1053

    Article  PubMed  CAS  Google Scholar 

  • Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF (1992) Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256:668–670

    Article  PubMed  CAS  Google Scholar 

  • Tuveson DA, Shaw AT, Willis NA, Silver DP, Jackson EL, Chang S, Mercer KL, Grochow R, Hock H, Crowley D, Hingorani SR, Zaks T, King C, Jacobetz MA, Wang L, Bronson RT, Orkin SH, DePinho RA, Jacks T (2004) Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 5:375–387

    Article  PubMed  CAS  Google Scholar 

  • Wasan HS, Novelli M, Bee J, Bodmer WF (1997) Dietary fat influences on polyp phenotype in multiple intestinal neoplasia mice. Proc Natl Acad Sci U S A 94:3308–3313

    Article  PubMed  CAS  Google Scholar 

  • Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–18

    Article  PubMed  CAS  Google Scholar 

  • Williamson SL, Kartheuser A, Coaker J, Kooshkghazi MD, Fodde R, Burn J, Mathers JC (1999) Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months. Carcinogenesis 20:805–810

    Article  PubMed  CAS  Google Scholar 

  • Yamauchi K, Yang M, Jiang P, Yamamoto N, Xu M, Amoh Y, Tsuji K, Bouvet M, Tsuchiya H, Tomita K, Moossa AR, Hoffman RM (2005) Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration. Cancer Res 65:4246–4252

    Article  PubMed  CAS  Google Scholar 

  • Yang K, Edelmann W, Fan K, Lau K, Leung D, Newmark H, Kucherlapati R, Lipkin M (1998) Dietary modulation of carcinoma development in a mouse model for human familial adenomatous polyposis. Cancer Res 58:5713–5717

    PubMed  CAS  Google Scholar 

  • Yang M, Reynoso J, Jiang P, Li L, Moossa AR, Hoffman RM (2004) Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors. Cancer Res 64:8651–8656

    Article  PubMed  CAS  Google Scholar 

  • Yang M, Jiang P, Yamamoto N, Li L, Geller J, Moossa AR, Hoffman RM (2005) Real-time whole-body imaging of an orthotopic metastatic prostate cancer model expressing red fluorescent protein. Prostate 62:374–379

    Article  PubMed  Google Scholar 

  • Zhu Y, Richardson JA, Parada LF, Graff JM (1998) Smad3 mutant mice develop metastatic colorectal cancer. Cell 94:703–714

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Equipe de Morphogenèse et Signalisation cellulaires, UMR 144 CNRS, Institut Curie, 25 rue d’Ulm, 75248, Paris Cedex 05, France

    D. Vignjevic, S. Fre, D. Louvard & S. Robine

Authors
  1. D. Vignjevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Fre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Louvard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Robine
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Interfakultäres Institut für Biochemie (IFIB) Signaltransduktion — transgene Modelle, Universität Tübingen, Hoppe-Seyler-Str. 4, 72076, Tübingen, Germany

    Robert Feil

  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1, rue Laurent Fries, 67404, Illkirch, France

    Daniel Metzger

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Vignjevic, D., Fre, S., Louvard, D., Robine, S. (2007). Conditional Mouse Models of Cancer. In: Feil, R., Metzger, D. (eds) Conditional Mutagenesis: An Approach to Disease Models. Handbook of Experimental Pharmacology, vol 178. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-35109-2_11

Download citation

Publish with us

Policies and ethics

Search

Navigation