Abstract

This new R01 application, currently in its 4th version seeks to understand the cellular and molecular mechanisms of human benign prostatic hyperplasia. The central hypothesis is that the growth and differentiation of the prostate is regulated by mesenchyme-epithelial interactions mediated by the local production and action of peptide growth factors such as TGFa, TGFB and KGF.
Two specific aims are planned to test this hypothesis.
The first aim i s to characterize a human cell line (BPH-1) that was generated by SV-40 large T antigen transformation of epithelial cells obtained from a BPH specimen. The characterization of these cells will include the testing for the expression of cytokeratins, androgen receptor, and prostate-specific secretory proteins. In addition, the effects of various growth factors on this cell line and the regulation of growth factor production by androgens will also be studied.
The second aim i s to investigate the role of mesenchyme-epithelial interaction in the regulation of the growth and development of the prostate. Tissue recombinants will be grown in athymic nude mice. Growth kinetics, tissue morphology and the expression of markers of prostatic differentiation as well as growth factor expression will be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK045861-01A3
Application #
2145101
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1994-09-30
Project End
1998-08-31
Budget Start
1994-09-30
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Urology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Cunha, Gerald R; Hayward, Simon W; Wang, Y Z et al. (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1-10
Cunha, Gerald R; Hayward, Simon W; Wang, Y Z (2002) Role of stroma in carcinogenesis of the prostate. Differentiation 70:473-85
Cunha, Gerald R; Matrisian, Lynn M (2002) It's not my fault, blame it on my microenvironment. Differentiation 70:469-72
Hayward, S W; Cunha, G R (2000) The prostate: development and physiology. Radiol Clin North Am 38:14-Jan
Tanji, N; Rahman, S A; Terada, N et al. (2000) Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro. Int J Androl 23:58-64
Olumi, A F; Grossfeld, G D; Hayward, S W et al. (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002-11
Perinchery, G; Bukurov, N; Nakajima, K et al. (1999) Loss of two new loci on chromosome 8 (8p23 and 8q12-13) in human prostate cancer. Int J Oncol 14:495-500
Lipschutz, J H; Fukami, H; Yamamoto, M et al. (1999) Clonality of urogenital organs as determined by analysis of chimeric mice. Cells Tissues Organs 165:57-66
Foster, B A; Cunha, G R (1999) Efficacy of various natural and synthetic androgens to induce ductal branching morphogenesis in the developing anterior rat prostate. Endocrinology 140:318-28
Thomson, A A; Cunha, G R (1999) Prostatic growth and development are regulated by FGF10. Development 126:3693-701

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