Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Nov;72(5):1189–1193. doi: 10.1038/bjc.1995.484

Mammary cancer in transgenic mice expressing insulin-like growth factor II (IGF-II)

P Bates 1, R Fisher 1, A Ward 1, L Richardson 1, D J Hill 1, C F Graham 1
PMCID: PMC2033962  PMID: 7577466

Abstract

The effect of insulin-like growth factor II (IGF-II) on tumour development in the mouse mammary gland was studied. To promote extra IGF-II expression in the mammary gland, sheep beta-lactoglobulin regulatory elements were attached to the coding regions of the mouse Igf-2 gene and injected into the pronuclei of mouse zygotes. Mammary tumours developed in each of the four independent lines of mice which expressed transgene IGF-II in the gland. Tumours from two of the lines grew after transplantation to both male and female hosts. Primary tumours contained stromal and epithelial regions, but the tumours were dominated by mammary adenocarcinoma after transplantation. The tumours expressed high levels of Igf-2 mRNA transcribed from the integrated transgenes.

Full text

PDF
1189

Images in this article

1191Figure 2
on p.1191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ali S., Clark A. J. Characterization of the gene encoding ovine beta-lactoglobulin. Similarity to the genes for retinol binding protein and other secretory proteins. J Mol Biol. 1988 Feb 5;199(3):415–426. doi: 10.1016/0022-2836(88)90614-6. [DOI] [PubMed] [Google Scholar]
  2. Baker J., Liu J. P., Robertson E. J., Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993 Oct 8;75(1):73–82. [PubMed] [Google Scholar]
  3. Berns E. M., Klijn J. G., van Staveren I. L., Portengen H., Foekens J. A. Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. Cancer Res. 1992 Feb 15;52(4):1036–1039. [PubMed] [Google Scholar]
  4. Biddle C., Li C. H., Schofield P. N., Tate V. E., Hopkins B., Engstrom W., Huskisson N. S., Graham C. F. Insulin-like growth factors and the multiplication of Tera-2, a human teratoma-derived cell line. J Cell Sci. 1988 Jul;90(Pt 3):475–484. doi: 10.1242/jcs.90.3.475. [DOI] [PubMed] [Google Scholar]
  5. Breier B. H., Milsom S. R., Blum W. F., Schwander J., Gallaher B. W., Gluckman P. D. Insulin-like growth factors and their binding proteins in plasma and milk after growth hormone-stimulated galactopoiesis in normally lactating women. Acta Endocrinol (Copenh) 1993 Nov;129(5):427–435. doi: 10.1530/acta.0.1290427. [DOI] [PubMed] [Google Scholar]
  6. Brünner N., Moser C., Clarke R., Cullen K. IGF-I and IGF-II expression in human breast cancer xenografts: relationship to hormone independence. Breast Cancer Res Treat. 1992;22(1):39–45. doi: 10.1007/BF01833332. [DOI] [PubMed] [Google Scholar]
  7. Callahan R., Salomon D. S. Oncogenes, tumour suppressor genes and growth factors in breast cancer: novel targets for diagnosis, prognosis and therapy. Cancer Surv. 1993;18:35–56. [PubMed] [Google Scholar]
  8. Christofori G., Hanahan D. Molecular dissection of multi-stage tumorigenesis in transgenic mice. Semin Cancer Biol. 1994 Feb;5(1):3–12. [PubMed] [Google Scholar]
  9. Christofori G., Naik P., Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature. 1994 Jun 2;369(6479):414–418. doi: 10.1038/369414a0. [DOI] [PubMed] [Google Scholar]
  10. Conover C. A., Clarkson J. T., Bale L. K. Insulin-like growth factor-II enhancement of human fibroblast growth via a nonreceptor-mediated mechanism. Endocrinology. 1994 Jul;135(1):76–82. doi: 10.1210/endo.135.1.8013394. [DOI] [PubMed] [Google Scholar]
  11. Conover C. A., Kiefer M. C., Zapf J. Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies. J Clin Invest. 1993 Mar;91(3):1129–1137. doi: 10.1172/JCI116272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Da Costa T. H., Williamson D. H., Ward A., Bates P., Fisher R., Richardson L., Hill D. J., Robinson I. C., Graham C. F. High plasma insulin-like growth factor-II and low lipid content in transgenic mice: measurements of lipid metabolism. J Endocrinol. 1994 Dec;143(3):433–439. doi: 10.1677/joe.0.1430433. [DOI] [PubMed] [Google Scholar]
  14. DeChiara T. M., Efstratiadis A., Robertson E. J. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature. 1990 May 3;345(6270):78–80. doi: 10.1038/345078a0. [DOI] [PubMed] [Google Scholar]
  15. Donovan S. M., Hintz R. L., Rosenfeld R. G. Insulin-like growth factors I and II and their binding proteins in human milk: effect of heat treatment on IGF and IGF binding protein stability. J Pediatr Gastroenterol Nutr. 1991 Oct;13(3):242–253. doi: 10.1097/00005176-199110000-00002. [DOI] [PubMed] [Google Scholar]
  16. Donovan S. M., Hintz R. L., Wilson D. M., Rosenfeld R. G. Insulin-like growth factors I and II and their binding proteins in rat milk. Pediatr Res. 1991 Jan;29(1):50–55. doi: 10.1203/00006450-199101000-00010. [DOI] [PubMed] [Google Scholar]
  17. Edwards P. A., Ward J. L., Bradbury J. M. Alteration of morphogenesis by the v-myc oncogene in transplants of mammary gland. Oncogene. 1988 Apr;2(4):407–412. [PubMed] [Google Scholar]
  18. Francis G. L., Upton F. M., Ballard F. J., McNeil K. A., Wallace J. C. Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form. Biochem J. 1988 Apr 1;251(1):95–103. doi: 10.1042/bj2510095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Guenette R. S., Corbeil H. B., Léger J., Wong K., Mézl V., Mooibroek M., Tenniswood M. Induction of gene expression during involution of the lactating mammary gland of the rat. J Mol Endocrinol. 1994 Feb;12(1):47–60. doi: 10.1677/jme.0.0120047. [DOI] [PubMed] [Google Scholar]
  20. Hall J. M., Lee M. K., Newman B., Morrow J. E., Anderson L. A., Huey B., King M. C. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990 Dec 21;250(4988):1684–1689. doi: 10.1126/science.2270482. [DOI] [PubMed] [Google Scholar]
  21. Harrington E. A., Bennett M. R., Fanidi A., Evan G. I. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 1994 Jul 15;13(14):3286–3295. doi: 10.1002/j.1460-2075.1994.tb06630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Harris S., Ali S., Anderson S., Archibald A. L., Clark A. J. Complete nucleotide sequence of the genomic ovine beta-lactoglobulin gene. Nucleic Acids Res. 1988 Nov 11;16(21):10379–10380. doi: 10.1093/nar/16.21.10379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Haselbacher G. K., Irminger J. C., Zapf J., Ziegler W. H., Humbel R. E. Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1104–1106. doi: 10.1073/pnas.84.4.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hill D. J. Relative abundance and molecular size of immunoreactive insulin-like growth factors I and II in human fetal tissues. Early Hum Dev. 1990 Jan;21(1):49–58. doi: 10.1016/0378-3782(90)90110-5. [DOI] [PubMed] [Google Scholar]
  25. Hébert E., Herbelin C., Bougnoux P. Analysis of the IGF-II receptor gene copy number in breast carcinoma. Br J Cancer. 1994 Jan;69(1):120–124. doi: 10.1038/bjc.1994.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee J. E., Tantravahi U., Boyle A. L., Efstratiadis A. Parental imprinting of an Igf-2 transgene. Mol Reprod Dev. 1993 Aug;35(4):382–390. doi: 10.1002/mrd.1080350411. [DOI] [PubMed] [Google Scholar]
  27. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Milazzo G., Giorgino F., Damante G., Sung C., Stampfer M. R., Vigneri R., Goldfine I. D., Belfiore A. Insulin receptor expression and function in human breast cancer cell lines. Cancer Res. 1992 Jul 15;52(14):3924–3930. [PubMed] [Google Scholar]
  29. Newell S., Ward A., Graham C. Discriminating translation of insulin-like growth factor-II (IGF-II) during mouse embryogenesis. Mol Reprod Dev. 1994 Nov;39(3):249–258. doi: 10.1002/mrd.1080390302. [DOI] [PubMed] [Google Scholar]
  30. Nielsen F. C. The molecular and cellular biology of insulin-like growth factor II. Prog Growth Factor Res. 1992;4(3):257–290. doi: 10.1016/0955-2235(92)90023-b. [DOI] [PubMed] [Google Scholar]
  31. Peyrat J. P., Bonneterre J. Type 1 IGF receptor in human breast diseases. Breast Cancer Res Treat. 1992;22(1):59–67. doi: 10.1007/BF01833334. [DOI] [PubMed] [Google Scholar]
  32. Rathjen P. D., Nichols J., Toth S., Edwards D. R., Heath J. K., Smith A. G. Developmentally programmed induction of differentiation inhibiting activity and the control of stem cell populations. Genes Dev. 1990 Dec;4(12B):2308–2318. doi: 10.1101/gad.4.12b.2308. [DOI] [PubMed] [Google Scholar]
  33. Rogler C. E., Yang D., Rossetti L., Donohoe J., Alt E., Chang C. J., Rosenfeld R., Neely K., Hintz R. Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. J Biol Chem. 1994 May 13;269(19):13779–13784. [PubMed] [Google Scholar]
  34. Rotwein P., Hall L. J. Evolution of insulin-like growth factor II: characterization of the mouse IGF-II gene and identification of two pseudo-exons. DNA Cell Biol. 1990 Dec;9(10):725–735. doi: 10.1089/dna.1990.9.725. [DOI] [PubMed] [Google Scholar]
  35. Sakakura T., Nishizuka Y., Dawe C. J. Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science. 1976 Dec 24;194(4272):1439–1441. doi: 10.1126/science.827022. [DOI] [PubMed] [Google Scholar]
  36. Wang T. C., Cardiff R. D., Zukerberg L., Lees E., Arnold A., Schmidt E. V. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994 Jun 23;369(6482):669–671. doi: 10.1038/369669a0. [DOI] [PubMed] [Google Scholar]
  37. Ward A., Bates P., Fisher R., Richardson L., Graham C. F. Disproportionate growth in mice with Igf-2 transgenes. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10365–10369. doi: 10.1073/pnas.91.22.10365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Webster M. A., Muller W. J. Mammary tumorigenesis and metastasis in transgenic mice. Semin Cancer Biol. 1994 Feb;5(1):69–76. [PubMed] [Google Scholar]
  39. Whitelaw C. B., Harris S., McClenaghan M., Simons J. P., Clark A. J. Position-independent expression of the ovine beta-lactoglobulin gene in transgenic mice. Biochem J. 1992 Aug 15;286(Pt 1):31–39. doi: 10.1042/bj2860031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wolff G. L. Body weight and cancer. Am J Clin Nutr. 1987 Jan;45(1 Suppl):168–180. doi: 10.1093/ajcn/45.1.168. [DOI] [PubMed] [Google Scholar]
  41. Wolff G. L., Roberts D. W., Galbraith D. B. Prenatal determination of obesity, tumor susceptibility, and coat color pattern in viable yellow (Avy/a) mice. The yellow mouse syndrome. J Hered. 1986 May-Jun;77(3):151–158. doi: 10.1093/oxfordjournals.jhered.a110206. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES