Skip to main content
SpringerLink
Log in

Potential Use of Transgenic Mice in Chemoprevention Studies

  • Chapter
Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 852 Accesses

Abstract

An oncomouse is a transgenic mouse in which the germline has been manipulated to overexpress certain genes or to delete certain genes so that the resulting mice will be more susceptible to developing cancer. For example, if a mutated copy of the epidermal growth factor receptor (EGFR)2/neu oncogene is placed on an murine mammary tumorvirus (MMTV) promoter (which is preferentially expressed in mammary epithelial cells), the resulting mice develop mammary tumors (1). In addition, if specific genes are knocked out—e.g., p53 in the germline of the mouse—the resulting animals will preferentially develop certain forms of cancer (2). Many of the earlier knockout models entailed knockout of the gene during embryogenesis and in all tissues. More sophisticated methods currently available allow knockout (or expression) of genes in very specific target cells (3) and at specific times during development. Furthermore, by crossbreeding transgenic mice, one may be able to make highly specific compound mice that are a more nearly “ ideal” model of human cancer (4).

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight 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

  1. Muller W, Sinn E, Pattengale PK, et al. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 1988;54:105–115.

    Article  PubMed  CAS  Google Scholar 

  2. Donehower LA. The p53-deficient mouse: a model for basic and applied cancer studies. Semin Cancer Biol 1996;7: 269–278.

    Article  PubMed  CAS  Google Scholar 

  3. Deng CX, Brodie SG. Knockout models and mammary tumorigenesis. Semin Cancer Biol 2001;11:387–394.

    Article  PubMed  CAS  Google Scholar 

  4. 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: 37–43.

    Article  PubMed  CAS  Google Scholar 

  5. Fisher B, Constantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–1388.

    Article  PubMed  CAS  Google Scholar 

  6. Umar A, Viner J, Hawk E. The future of colon cancer prevention. Ann NY Acad Sci 2001;952: 88–108.

    Article  PubMed  CAS  Google Scholar 

  7. Wang JS, Huang T, Su J, et al. Hepatocellular carcinoma and alflatoxin exposure in Zhuqing Village, Fusui County, People’s Republic of China. Cancer Epidemiol Biomarkers Prev 2001;10: 143–146.

    PubMed  CAS  Google Scholar 

  8. Egner PA, Wang JB, Zhu YR, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci USA 2001;98: 14601–14606.

    Article  PubMed  CAS  Google Scholar 

  9. Cardiff RD, Anver MR, Gusterson BA, et al. The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene 2000;19:968–988.

    Article  PubMed  CAS  Google Scholar 

  10. Desai KV, Xiao N, Wang W, et al. Initiating oncogenic event determines gene-expression patterns of human breast cancer models. Proc Natl Acad Sci USA 2002;14:6967–6972.

    Article  CAS  Google Scholar 

  11. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406:747–752.

    Article  PubMed  CAS  Google Scholar 

  12. van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002;415:530–536.

    Article  Google Scholar 

  13. Piccart-Gephart MJ. Herceptin: the future in adjuvant breast cancer therapy. Anticancer Drugs 2001; 4:S27–S33.

    Google Scholar 

  14. Raghow S, Hooshdaran MZ, Katiyar S, Steiner MS. Toremifene prevents prostate cancer in the transgenic adenocarcinoma of the mouse prostate model. Cancer Res 2002; 62:1370–1376.

    PubMed  CAS  Google Scholar 

  15. Raghow S, Kuliyev E, Steakley M, et al. Efficacious chemoprevention of primary prostate cancer by flutamide in an autochthonous transgenic model. Cancer Res 2000;60: 4093–4097.

    PubMed  CAS  Google Scholar 

  16. Zhang J, Thomas TZ, Kasper S, Matusik RJ. A small composite probasin promoter confers high levels of prostatespecific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo. Endocrinology 2000;141:4698–4710.

    Article  PubMed  CAS  Google Scholar 

  17. Lal G, Ash C, Hay K, et al. Suppression of intestinal polyps in MSH-2 deficient and non-MSH-2 deficient multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Cancer Res 2001;61: 6131–6136.

    PubMed  CAS  Google Scholar 

  18. Greenberg NM, De Mayo F, Finegold MJ, et al. Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 1995;92: 3439–3443.

    Article  PubMed  CAS  Google Scholar 

  19. Maroulakou IG, Avner M, Garrett L, Green J. Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci USA 1994;91: 11236–11240.

    Article  PubMed  CAS  Google Scholar 

  20. Masumori N, Thomas TZ, Chaurand P, et al. A probasinlarge T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res 2001;61:2239–2249.

    PubMed  CAS  Google Scholar 

  21. Wechter WJ, Leipold. DD, Murray ED Jr, et al. E-7869 (Rflurbiprofen) inhibits progression of prostate cancer in the TRAMP mouse. Cancer Res 2000;60:2203–2208.

    PubMed  CAS  Google Scholar 

  22. Gupta S, Ahmad N, Maregno SR, et al. Chemoprevention of prostate carcinogenesis by alpha-difluoromethylornithine in TRAMP mice. Cancer Res 2000;60:5125–5133.

    PubMed  CAS  Google Scholar 

  23. Gupta S, Hastak K, Ahmad N, et al. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci USA 2001;98: 10350–10355.

    Article  PubMed  CAS  Google Scholar 

  24. DiGiovanni J, Kiguchi K, Frijhoff A, et al. Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc Natl Acad Sci USA 2000;28:3455–3460.

    Article  Google Scholar 

  25. Abdulkadir SA, Magee JA, Peters TJ, et al. Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia. Mol Cell Biol 2002;22:1495–1503.

    Article  CAS  Google Scholar 

  26. Bhatia-Gaur R, Donjacour AA, Sciavolino PJ, et al. Roles for Nkx3.1 in prostate development and cancer. Genes Dev 1999;13:966–977.

    Article  PubMed  CAS  Google Scholar 

  27. Kim MJ, Cardiff RD, Desai N, et al. Cooperativity of Nkx3.1 and PTEN loss of function in a mouse model of prostate carcinogenesis. Proc Natl Acad Sci USA 2002;99:2884–2889.

    Article  PubMed  CAS  Google Scholar 

  28. Cardiff RD, Bern HA, Faulkin LJ, et al. Contributions of mouse biology to breast cancer research. Comp Med 2002;52:12–31.

    PubMed  CAS  Google Scholar 

  29. Liu CH, Chang SH, Narko K, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 2001;276:18,563–18,569.

    Article  PubMed  CAS  Google Scholar 

  30. Wang B, Kennan WS, Yasukawa-Barnes J, et al. Difference in the response of neu and ras oncogene-induced rat mammary carcinomas to early and late ovariectomy. Cancer Res 1992;52:4102–4105.

    PubMed  CAS  Google Scholar 

  31. Pupa SM, Invernizzi AM, Forti S, et al. Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by DNA vaccination. Gene Ther 2001;8:75–79.

    Article  PubMed  CAS  Google Scholar 

  32. Rao GN, Ney E, Herbert RA. Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene. Breast Cancer Res Treat 1998;48: 265–271.

    Article  PubMed  CAS  Google Scholar 

  33. Wu K, Zhang Y, Celestino J, et al. The RXR selective retinoid, LGD1069, prevents tumor development in MMTV erb B2 transgenic mice. Cancer Res 2002;62:6376–6380.

    PubMed  CAS  Google Scholar 

  34. Wu K, Kim HT, Rodriguez JL, et al. Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069. Cancer Epidemiol Biomarkers Prev 2002;11:467–474.

    PubMed  CAS  Google Scholar 

  35. Green JE, Shibata MA, Shibata E, et al. 2-Difluromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice. Cancer Res 2001;61:7449–7455.

    PubMed  CAS  Google Scholar 

  36. Yokoyama Y, Green JE, Sukhatme VP, Ramakrishnan S. Effects of endostatin on spontaneous tumorigenesis of mammary adenocarcinoma in a transgenic mouse model. Cancer Res 2000;60:4362–4365.

    PubMed  CAS  Google Scholar 

  37. Bachelier R, Li C, Xu X, et al. Decreased mammary tumor incidence in conditional BRCA1 mutant mice after bilateral oophorectomy. Proc Am Assoc Cancer Res 2002;43:512, abst. no. 2542.

    Google Scholar 

  38. 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: 418–425.

    Article  PubMed  CAS  Google Scholar 

  39. Zhang Z, Liu Q, Lantry LE, et al. A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inisitol and chemotherapeutic agents taxol or adriamycin. Cancer Res 2000;60:901–907.

    PubMed  CAS  Google Scholar 

  40. You M, Wang Y, Stoner G, et al. Parental bias of Ki-Ras oncogenes detected in lung tumors from mouse hybrids. Proc Natl Acad Sci USA 1992;89:5804–5808.

    Article  PubMed  CAS  Google Scholar 

  41. Witschi H, Uyeminami D, Moran D, Espiritu I. Chemopreven-tion of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure. Carcinogenesis 2000;21: 977–982.

    Article  PubMed  CAS  Google Scholar 

  42. DeFlora S, Balansky RM, D’Agostini F, et al. Molecular alternations and lung tumors in p53 mutant mice exposed to cigarette smoke. Cancer Res 2003;63:793–800.

    CAS  Google Scholar 

  43. Wikenheiser KA, Whitsett JA. Tumor progression and cellular differentiation of pulmonary adenocarcinomas in SV40 large T antigen transgenic mice. Am J Respir Cell Mol Biol 1997;16:713–723.

    PubMed  CAS  Google Scholar 

  44. Jackson EL, Willis N, Mercer K, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 2001;15:3243–3248.

    Article  PubMed  CAS  Google Scholar 

  45. Fisher GH, Wellen SL, Klimstra D, et al. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence or absence of tumor suppressor genes. Genes Dev 2001;15: 3249–3262.

    Article  PubMed  CAS  Google Scholar 

  46. Meuwissen R, Linn SC, Linnoila I, et al. Induction of small cell lung cancer in mice by somatic inactivation of both p53 and RB1 in a conditional mouse model. Cancer Cell 2003;4:181–189.

    Article  PubMed  CAS  Google Scholar 

  47. Wang Y, Zhang Z, Yan Y, et al. Achemically induced model for squamous cell carcinoma of the lung in mice: histopathology and strain susceptibility. Cancer Res 2004; 64:1647–1654.

    Article  PubMed  CAS  Google Scholar 

  48. Arbeit JM, Munger K, Howley PM, Hanahan D. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice. J Virol 1994;68:4358–4368.

    PubMed  CAS  Google Scholar 

  49. Arbeit JM, Riley RR, Huey B, et al. Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice. Cancer Res 1999;59: 3610–3620.

    PubMed  CAS  Google Scholar 

  50. Jin L, Qi M, Chen DZ, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV 16) transgenic mice. Cancer Res 1999;59:3391–3397.

    Google Scholar 

  51. Hursting SD, Perkins SN, Donehower LA, Davis BJ. Cancer prevention studies in p53-deficient mice. Toxicol Pathol 2001;29:137–141.

    Article  PubMed  CAS  Google Scholar 

  52. Lubet RA, Zhang Z, Wiseman RW, You M. Use of p53 transgenic mice in the development of cancer models for multiple purposes. Exp Lung Res 2000;26:581–593.

    Article  PubMed  CAS  Google Scholar 

  53. Zhang Z, Li J, Lantry LE, et al. p53 Transgenic mice are highly susceptible to 1,2-dimethylhydrazine-induced uterine sarcomas. Cancer Res 2002;62:3024–3029.

    PubMed  CAS  Google Scholar 

  54. Zhang Z, Wang Y, Yao R, et al. Cancer chemopreventive activity of a mixture of Chinese herbs in mouse lung tumor models. Oncogen 2004;23:3841–3850

    Article  CAS  Google Scholar 

  55. Zhang Z, Wang Y, Lantry LE, et al. Farnesyltransferase inhibitors are potent lung cancer chemopreventive agents. Oncogene 2003;22:6257–6265.

    Article  PubMed  CAS  Google Scholar 

  56. Halberg RB, Katzung D, Hoff P, et al. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers. Proc Natl Acad Sci USA 2000;97:3461–3466.

    Article  PubMed  CAS  Google Scholar 

  57. Li B, Murphy KL, Laucirica R, et al. Atransgenic mouse model for mammary carcinogenesis. Oncogene 1998;16:997–1007

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Ronald A. Lubet PhD & Vernon E. Steele PhD, MPH

  2. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institutes, National Institutes of Health, Bethesda, MD

    Jeffrey Green MD

  3. The Siteman Cancer Center; Division of General Surgery, Washington University School of Medicine, St. Louis, MO

    Ming You MD, PhD

Authors
  1. Ronald A. Lubet PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey Green MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vernon E. Steele PhD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming You MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Biomedical Imaging Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Gary J. Kelloff MD

  2. Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Ernest T. Hawk MD, MPH

  3. CCS Associates, Mountain View, CA

    Caroline C. Sigman PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Lubet, R.A., Green, J., Steele, V.E., You, M. (2005). Potential Use of Transgenic Mice in Chemoprevention Studies. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59259-768-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-768-0_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-077-9

  • Online ISBN: 978-1-59259-768-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation