The cellular and molecular biological role of activin-A, a molecule recently found to be localized immunohistochemically and transcribed in a cell line of prostatic cancer, DU-145, will be studied in vivo and in vitro using techniques of in situ hybridization, Northern blotting analysis, and reverse transcription-polymerase chain reaction (RT-PCR). In addition, we will study the detailed biology of prostatic activin- A/inhibin in rats during development, under hormonal manipulation, as well as in primary cultures of epithelial cells or stromal cells because inhibin/activin-A was immunohistochemically localized in intact rat prostate. We will also attempt to investigate prostatic activin-A in cell lines of other human prostatic cancers. From the data obtained with all of these approaches, we will have a baseline of fundamental information about the role of activin-A/inhibin in prostatic cancer. This knowledge will enable us to explore the role of activin-A/inhibin as growth factors in growth and differentiation of the prostate and will be clinically useful in designing new approaches to treating prostatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047609-03
Application #
2147361
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1993-09-30
Project End
1997-08-31
Budget Start
1995-09-15
Budget End
1996-08-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Zheng, W; Luo, M P; Welt, C et al. (1998) Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer. Gynecol Oncol 69:23-31
Zhang, Z; Zhao, Y; Batres, Y et al. (1997) Regulation of growth and prostatic marker expression by activin A in an androgen-sensitive prostate cancer cell line LNCAP. Biochem Biophys Res Commun 234:362-5
Ying, S Y; Zhang, Z; Huang, G (1997) Expression and localization of inhibin/activin subunits and activin receptors in the normal rat prostate. Life Sci 60:397-401
Ying, S Y; Zhang, Z; Furst, B et al. (1997) Activins and activin receptors in cell growth. Proc Soc Exp Biol Med 214:114-22
Zhang, Z; Batres, Y; Ying, S Y (1996) Activin A inhibits growth and hexamethylene bisacetamide-induced differentiation in human retinoblastoma Y-79 cells. Anticancer Res 16:269-72
Ying, S Y; Zhang, Z (1996) Expression and localization of inhibin/activin subunits and activin receptors in MCF-7 cells, a human breast cancer cell line. Breast Cancer Res Treat 37:151-60
Ying, S Y; Li, S; Ishikawa, M et al. (1995) Immunohistochemical localization of inhibin in the retinal interphotoreceptor matrix. Exp Eye Res 60:585-90
Ying, C; Zhang, Z; Ying, S Y (1995) Expression and localization of activin beta A-subunit and activin receptors in TM3, a mouse Leydig cell line. Endocr Res 21:815-24
Zhang, Z; Ying, S Y (1995) Expression of activins and activin receptors in human retinoblastoma cell line Y-79. Cancer Lett 89:207-14
Ying, S Y; Li, S Q; Zhang, Z (1995) Expression and localization of inhibin alpha-subunit in rat retinal photoreceptor cells. Life Sci 57:45-52

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