This proposed study will focus on the investigation of cellular mechanisms of stromal-epithelial interaction in the rat prostate gland as an extension of our previously funded program which stressed on the study of tissue interactions in vivo. In this study, we will pursue two major objectives: 1. We will define the role of dihydrotestosterone (DHT) in stromal-epithelial interactions in the rat prostate gland. This goal will be accomplished first by establishing viable cell lines that represent rat prostatic epithelial, fibroblast, and smooth muscle cells. We will clone a DHT-responsive fibroblast cell line which will allow us to assess the role of fibroblast in regulating androgen-induced DNA synthesis and gene expression by the prostatic epithelium. The possible mechanism of """"""""indirect"""""""" action of DHT on growth and differentiation of prostatic epithelium mediated by prostatic fibroblast, in the form of growth factor(s). extracellular matrix and intracellular signals, will be examined. 2. We will take advantage of certain established specificities of fetal adult tissue interactions in the rat prostate gland to isolate a fetal urogenital sinus-derived growth factor(s) (UGSGF). We will employ an established prostatic cell culture system for the detection of UGSGF. The possibility that this growth factor may be closely related to the family of basic fibroblast growth factor will be investigated. In order to obtain this material in sufficient quantity and to purify it for other relevant biological studies (e.g., specificity, dose response relationship, interaction with DHT and other growth factors, UGSGF receptor(s) and in vivo growth and regenerative activity), we propose to use molecular biology techniques and to prepare monoclonal antibodies to facilitate our progress in achieving these goals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038649-06
Application #
2140608
Study Section
Pathology B Study Section (PTHB)
Project Start
1986-07-01
Project End
1995-11-30
Budget Start
1992-12-01
Budget End
1995-11-30
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Urology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Thalmann, G N; Sikes, R A; Chang, S M et al. (1996) Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer. J Natl Cancer Inst 88:794-801
Marengo, S R; Chung, L W (1994) An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl 15:277-86
Wu, H C; Hsieh, J T; Gleave, M E et al. (1994) Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int J Cancer 57:406-12
Thalmann, G N; Anezinis, P E; Chang, S M et al. (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54:2577-81
Zhau, H E; Pisters, L L; Hall, M C et al. (1994) Biomarkers associated with prostate cancer progression. J Cell Biochem Suppl 19:208-16
Zhau, H E; Hong, S J; Chung, L W (1994) A fetal rat urogenital sinus mesenchymal cell line (rUGM): accelerated growth and conferral of androgen-induced growth responsiveness upon a human bladder cancer epithelial cell line in vivo. Int J Cancer 56:706-14
Hoosein, N M; Logothetis, C J; Chung, L W (1993) Differential effects of peptide hormones bombesin, vasoactive intestinal polypeptide and somatostatin analog RC-160 on the invasive capacity of human prostatic carcinoma cells. J Urol 149:1209-13
Gleave, M E; Hsieh, J T; Wu, H C et al. (1993) Epidermal growth factor receptor-mediated autocrine and paracrine stimulation of human transitional cell carcinoma. Cancer Res 53:5300-7
Chung, L W (1993) Implications of stromal-epithelial interaction in human prostate cancer growth, progression and differentiation. Semin Cancer Biol 4:183-92
McDonnell, T J; Troncoso, P; Brisbay, S M et al. (1992) Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 52:6940-4

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