Home LiteratureArticle Details
PMID: 7724580 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Prostate cancer in a transgenic mouse.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 8 ·1995-04-11 ·Pages 3439-43

Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ, Rosen JM

Abstract

Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.

MeSH Terms
Androgen-Binding Protein/genetics Animals Antigens, Viral, Tumor/genetics Base Sequence Carcinoma/classification,genetics,pathology Disease Models, Animal Genes, Reporter Image Processing, Computer-Assisted Immunohistochemistry Male Mice Mice, Transgenic Molecular Sequence Data Promoter Regions, Genetic/genetics Prostatic Neoplasms/classification,genetics,pathology Recombinant Proteins Simian virus 40/genetics Tissue Distribution Tumor Suppressor Protein p53/isolation & purification
Chemicals
Androgen-Binding Protein Antigens, Viral, Tumor Recombinant Proteins Tumor Suppressor Protein p53 probasin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Greenberg N M
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
DeMayo F
Finegold M J
Medina D
Tilley W D
Aspinall J O
Cunha G R
Donjacour A A
Matusik R J
Rosen J M
References (42)
42 references, click to expand
  1. Spontaneous prostate adenocarcinomas in aged germfree Wistar rats.
    J Natl Cancer Inst. 1973 Oct;51(4):1235-41 PMID: 4745857
  2. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer.
    Cancer Res. 1994 May 15;54(10):2577-81 PMID: 8168083
  3. The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration.
    Cancer Res. 1977 Jun;37(6):1929-33 PMID: 858144
  4. T antigen is bound to a host protein in SV40-transformed cells.
    Nature. 1979 Mar 15;278(5701):261-3 PMID: 218111
  5. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.
    Cell. 1979 May;17(1):43-52 PMID: 222475
  6. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  7. Characterization and cloning of rat dorsal prostate mRNAs. Androgen regulation of two closely related abundant mRNAs.
    J Biol Chem. 1983 Sep 10;258(17):10731-7 PMID: 6193116
  8. Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors.
    Cell. 1984 Jun;37(2):367-79 PMID: 6327063
  9. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes.
    Nature. 1985 May 9-15;315(6015):115-22 PMID: 2986015
  10. Regulation of prostatic genes: role of androgens and zinc in gene expression.
    Biochem Cell Biol. 1986 Jun;64(6):601-7 PMID: 3741677
  11. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene.
    Cell. 1988 Jul 15;54(2):275-83 PMID: 2839300
  12. 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):230-9 PMID: 8170479
  13. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis.
    Nature. 1994 Jun 2;369(6479):414-8 PMID: 7910953
  14. Detection of discrete androgen receptor epitopes in prostate cancer by immunostaining: measurement by color video image analysis.
    Cancer Res. 1994 Aug 1;54(15):4096-102 PMID: 7518349
  15. Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.
    Mol Cell Biol. 1994 Sep;14(9):6244-52 PMID: 8065356
  16. Preferential overexpression of a 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development.
    Cell Growth Differ. 1994 Jul;5(7):711-21 PMID: 7947386
  17. Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11236-40 PMID: 7972041
  18. Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms.
    Lab Invest. 1995 Mar;72(3):283-90 PMID: 7534850
  19. Oncogene expression in prostate cancer: Dunning R3327 rat dorsal prostatic adenocarcinoma system.
    Prostate. 1988;13(4):263-72 PMID: 3217275
  20. Post-castration rebound of an androgen regulated prostatic gene.
    Mol Cell Biochem. 1988 Nov;84(1):3-15 PMID: 2466196
  21. Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ.
    Cell. 1989 Mar 24;56(6):917-30 PMID: 2538247
  22. Androgen-dependent human prostate cancer in nude mice. The PC-82 tumor model.
    Am J Clin Oncol. 1988;11 Suppl 2:S8-12 PMID: 3242388
  23. Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin gene.
    Cancer Res. 1989 Nov 1;49(21):6108-17 PMID: 2551499
  24. Induction of metachromasia in experimentally induced hyperplastic/hypertrophic changes in the prostate of the cynomolgus monkey (Macaca fascicularis).
    J Urol. 1989 Dec;142(6):1624-6 PMID: 2479780
  25. Cancer statistics, 1990.
    CA Cancer J Clin. 1990 Jan-Feb;40(1):9-26 PMID: 2104569
  26. Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A.
    Cell. 1990 Jan 12;60(1):167-76 PMID: 2153055
  27. Characterization of antibodies to androgen-dependent secretory proteins of the mouse dorsolateral prostate.
    Endocrinology. 1990 Mar;126(3):1343-54 PMID: 2307108
  28. The int-2 gene product acts as an epithelial growth factor in transgenic mice.
    EMBO J. 1990 Mar;9(3):907-13 PMID: 1690126
  29. Treatment of R-3327 prostate tumors with a somatostatin analogue (somatuline) as adjuvant therapy following surgical castration.
    Cancer Res. 1990 May 1;50(9):2646-50 PMID: 1970275
  30. Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7762-6 PMID: 2217208
  31. Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes.
    J Surg Oncol. 1991 Jan;46(1):31-6 PMID: 1986144
  32. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections.
    J Histochem Cytochem. 1991 Jun;39(6):741-8 PMID: 1709656
  33. The p53 tumour suppressor gene.
    Nature. 1991 Jun 6;351(6326):453-6 PMID: 2046748
  34. Transgenic models of tumor development.
    Science. 1991 Nov 22;254(5035):1161-7 PMID: 1957168
  35. Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene.
    Mol Endocrinol. 1993 Jan;7(1):23-36 PMID: 8446105
  36. Image analysis of androgen receptor immunostaining in metastatic prostate cancer. Heterogeneity as a predictor of response to hormonal therapy.
    Cancer. 1993 Apr 15;71(8):2574-80 PMID: 7680949
  37. Genetic predisposition and mesenchymal-epithelial interactions in ras+myc-induced carcinogenesis in reconstituted mouse prostate.
    Mol Carcinog. 1993;7(3):165-79 PMID: 8489712
  38. 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):1965-71 PMID: 8390039
  39. p53 oncogene mutations in three human prostate cancer cell lines.
    Prostate. 1993;23(2):123-34 PMID: 8104329
  40. Dietary fenretinide, a synthetic retinoid, decreases the tumor incidence and the tumor mass of ras+myc-induced carcinomas in the mouse prostate reconstitution model system.
    Cancer Res. 1993 Oct 1;53(19):4461-5 PMID: 8402613
  41. Immunohistochemical determination of p53 protein nuclear accumulation in prostatic adenocarcinoma.
    J Urol. 1994 May;151(5):1276-80 PMID: 8158773
  42. Spontaneous adenocarcinomas of the ventral prostate of aged A X C rats.
    J Natl Cancer Inst. 1975 Jul;55(1):177-80 PMID: 1159811
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.8.3439
Published
1995-04-11
Pages
3439-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42182
Subset
IM
Grants
NCI NIH HHS · CA58204 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.8.3439 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2