Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1994 Nov 8; 91(23): 11236–11240.

Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene.


A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. Female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Stewart TA, Pattengale PK, Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984 Oct;38(3):627–637. [PubMed]
  • Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986 May 23;45(4):485–495. [PubMed]
  • Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell. 1987 May 22;49(4):465–475. [PubMed]
  • Andres AC, Schönenberger CA, Groner B, Hennighausen L, LeMeur M, Gerlinger P. Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1299–1303. [PMC free article] [PubMed]
  • Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell. 1988 Nov 18;55(4):619–625. [PubMed]
  • Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988 Jul 1;54(1):105–115. [PubMed]
  • Bouchard L, Lamarre L, Tremblay PJ, Jolicoeur P. Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell. 1989 Jun 16;57(6):931–936. [PubMed]
  • Matsui Y, Halter SA, Holt JT, Hogan BL, Coffey RJ. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell. 1990 Jun 15;61(6):1147–1155. [PubMed]
  • Muller WJ, Lee FS, Dickson C, Peters G, Pattengale P, Leder P. The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J. 1990 Mar;9(3):907–913. [PMC free article] [PubMed]
  • Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell. 1990 Jun 15;61(6):1121–1135. [PubMed]
  • Jhappan C, Stahle C, Harkins RN, Fausto N, Smith GH, Merlino GT. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell. 1990 Jun 15;61(6):1137–1146. [PubMed]
  • Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev. 1992 Mar;6(3):345–355. [PubMed]
  • Tzeng YJ, Guhl E, Graessmann M, Graessmann A. Breast cancer formation in transgenic animals induced by the whey acidic protein SV40 T antigen (WAP-SV-T) hybrid gene. Oncogene. 1993 Jul;8(7):1965–1971. [PubMed]
  • Pollard M, Luckert PH. Transplantable metastasizing prostate adenocarcinomas in rats. J Natl Cancer Inst. 1975 Mar;54(3):643–649. [PubMed]
  • Pollard M, Luckert PH. Autochthonous prostate adenocarcinomas in Lobund-Wistar rats: a model system. Prostate. 1987;11(3):219–227. [PubMed]
  • Pollard M, Luckert PH, Snyder DL. The promotional effect of testosterone on induction of prostate-cancer in MNU-sensitized L-W rats. Cancer Lett. 1989 Jun;45(3):209–212. [PubMed]
  • Beckman WC, Jr, Jacokes AL, Camps JL, Jr, Cook RL, Siegal GP. Analysis of changes in rat prostate carcinoma following hormone deprivation. Am J Pathol. 1987 Sep;128(3):566–572. [PMC free article] [PubMed]
  • Waalkes MP, Rehm S, Riggs CW, Bare RM, Devor DE, Poirier LA, Wenk ML, Henneman JR, Balaschak MS. Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of tumor induction in the prostate and testes and at the injection site. Cancer Res. 1988 Aug 15;48(16):4656–4663. [PubMed]
  • Thompson TC, Southgate J, Kitchener G, Land H. Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ. Cell. 1989 Mar 24;56(6):917–930. [PubMed]
  • Ward JM, Reznik G, Stinson SF, Lattuada CP, Longfellow DG, Cameron TP. Histogenesis and morphology of naturally occurring prostatic carcinoma in the ACI/segHapBR rat. Lab Invest. 1980 Dec;43(6):517–522. [PubMed]
  • Ito N, Shirai T, Tagawa Y, Nakamura A, Fukushima S. Variation in tumor yield in the prostate and other target organs of the rat in response to varied dosage and duration of administration of 3,2'-dimethyl-4-aminobiphenyl. Cancer Res. 1988 Aug 15;48(16):4629–4632. [PubMed]
  • Shirai T, Tamano S, Kato T, Iwasaki S, Takahashi S, Ito N. Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate. Cancer Res. 1991 Feb 15;51(4):1264–1269. [PubMed]
  • Buttyan R, Slawin K. Rodent models for targeted oncogenesis of the prostate gland. Cancer Metastasis Rev. 1993 Mar;12(1):11–19. [PubMed]
  • Cohen MB, Heidger PM, Lubaroff DM. Gross and microscopic pathology of induced prostatic complex tumors arising in Lobund-Wistar rats. Cancer Res. 1994 Feb 1;54(3):626–628. [PubMed]
  • Parker MG, White R, Hurst H, Needham M, Tilly R. Prostatic steroid-binding protein. Isolation and characterization of C3 genes. J Biol Chem. 1983 Jan 10;258(1):12–15. [PubMed]
  • Hurst HC, Parker MG. Rat prostatic steroid binding protein: DNA sequence and transcript maps of the two C3 genes. EMBO J. 1983;2(5):769–774. [PMC free article] [PubMed]
  • Hsu SM, Soban E. Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem. 1982 Oct;30(10):1079–1082. [PubMed]
  • Tan JA, Marschke KB, Ho KC, Perry ST, Wilson EM, French FS. Response elements of the androgen-regulated C3 gene. J Biol Chem. 1992 Mar 5;267(7):4456–4466. [PubMed]
  • Allison J, Zhang YL, Parker MG. Tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein in transgenic mice. Mol Cell Biol. 1989 May;9(5):2254–2257. [PMC free article] [PubMed]
  • Greenberg NM, DeMayo FJ, Sheppard PC, Barrios R, Lebovitz R, Finegold M, Angelopoulou R, Dodd JG, Duckworth ML, Rosen JM, et al. The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol Endocrinol. 1994 Feb;8(2):230–239. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...