Utilizing a series of novel murine recombinant retroviruses which contain the human androgen receptor (hAR) gene, the v-gagmyc oncogene, TGF-b genes, and the b-FGF gene together with the bacterial beta-galactosidase gene (for visualization in tissue sections), the effects of overexpressing these genes on the growth and differentiation of the mouse prostate will be studied. The investigators will test the stromal-epithelial interaction hypothesis by introducing these genes specifically into mesenchymal cells and combining them with either normal, genetically unaltered, or myc-infected epithelium. By this approach both the gene specificity and gene complementarity with respect to stromal-epithelial interactions will be addressed. They will further probe the mechanism(s) of BPH by a combined immunohistochemical/molecular approach that will differentiate exogenous and endogenous growth factor expression and demonstrate possible field effects resulting from positive autoregulation of growth factor expression, shown previously to occur in the case of TGF-b. These studies, as well as northern and southern blotting analysis, will further test the hypothesis that BPH nodules result from growth factor recruitment of adjacent normal cells and/or clonal expansion by altered cells with enhanced growth potential.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043523-02
Application #
3244899
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1991-09-15
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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Timme, T L; Yang, G; Truong, L D et al. (1995) Transforming growth factor-beta localization during mouse prostate morphogenesis and in prostatic growth abnormalities. World J Urol 13:324-8
Baley, P A; Yoshida, K; Qian, W et al. (1995) Progression to androgen insensitivity in a novel in vitro mouse model for prostate cancer. J Steroid Biochem Mol Biol 52:403-13
Timme, T L; Truong, L D; Merz, V W et al. (1994) Mesenchymal-epithelial interactions and transforming growth factor-beta expression during mouse prostate morphogenesis. Endocrinology 134:1039-45
Thompson, T C; Truong, L D; Timme, T L et al. (1993) Transgenic models for the study of prostate cancer. Cancer 71:1165-71
Thompson, T C; Timme, T L; Kadmon, D et al. (1993) Genetic predisposition and mesenchymal-epithelial interactions in ras+myc-induced carcinogenesis in reconstituted mouse prostate. Mol Carcinog 7:165-79
Lu, X; Park, S H; Thompson, T C et al. (1992) Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation. Cell 70:153-61
Thompson, T C; Truong, L D; Timme, T L et al. (1992) Transforming growth factor beta 1 as a biomarker for prostate cancer. J Cell Biochem Suppl 16H:54-61