Our central theme is to study the cellular and chemical aspects of benign prostatic growth, because benign prostatic hyperplasia (BPH) is the major health concern in aging black and white populations in the U.S. and because the cellular and chemical etiology of BPH remains unknown. The Center consists of 4 research projects and 2 core units. Project 1 proposes 2 hypotheses. The first hypothesis states that cellular activities in the transition zone are different from those in the central and peripheral zones of the human prostate. The second hypothesis states that prostatic growth is the result of stromal-epithelial interaction that is mediated through the production of various growth factors. Project 2 postulates the existence of a non-androgenic role of the testis in prostatic growth. In vivo and in vitro studies are proposed. In vivo studies will identify the systemic non-androgenic factor(s) which is secreted by the testis into the circulation; while in vitro studies will identify the locally affecting factor(s) which is present in the seminal plasma. Project 3 will characterize the role of innervation in prostatic structure and function. Selective denervation experiments in rats and the effect of replacement of various neurotransmitters on the prostate will be tested. Regional variation in innervation along the prostatic ductal system will also be studied. Project 4 intends to study prostatic growth in animal systems to complement findings in the human prostate. The use of animal systems will allow a greater degree of flexibility in manipulating host conditions. In vivo experiments will study changes in cellular growth, differentiation, and degeneration along the newly identified prostatic ductal system. In vitro experiments will study the effect of tissue extracts from the prostate under conditions of rapid growth and growth arrest. Core Unit 1 is the administrative core responsible for the overall coordination and management of the Center. The core consists of the administrative, statistical, and human tissue procurement components. Core Unit 2 is the centralized laboratory facility which includes the two-dimensional electrophoresis laboratory and the histology laboratory. This proposal represents an extension of our previous study. Information generated from these studies will provide further insights into the cellular and chemical basis of benign prostatic growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK039250-07
Application #
3105850
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1987-09-01
Project End
1997-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Organized Research Units
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
Ilio, K Y; Nemeth, J A; Sensibar, J A et al. (2000) Prostatic ductal system in rats: changes in regional distribution of extracellular matrix proteins during castration-induced regression. Prostate 43:10-Mar
Kassen, A E; Sensibar, J A; Sintich, S M et al. (2000) Autocrine effect of DHT on FGF signaling and cell proliferation in LNCaP cells: role of heparin/heparan-degrading enzymes. Prostate 44:124-32
Lee, C; Sintich, S M; Mathews, E P et al. (1999) Transforming growth factor-beta in benign and malignant prostate. Prostate 39:285-90
Sensibar, J A; Pruden, S J; Kasjanski, R Z et al. (1999) Differential growth rates in stromal cultures of human prostate derived from patients of varying ages. Prostate 38:110-7
Kim, I Y; Ahn, H J; Lang, S et al. (1998) Loss of expression of transforming growth factor-beta receptors is associated with poor prognosis in prostate cancer patients. Clin Cancer Res 4:1625-30
Kim, I Y; Zelner, D J; Lee, C (1998) The conventional transforming growth factor-beta (TGF-beta) receptor type I is not required for TGF-beta 1 signaling in a human prostate cancer cell line, LNCaP. Exp Cell Res 241:151-60
Grayhack, J T; Kozlowski, J M; Lee, C (1998) The pathogenesis of benign prostatic hyperplasia: a proposed hypothesis and critical evaluation. J Urol 160:2375-80
Sherwood, E R; Van Dongen, J L; Wood, C G et al. (1998) Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells. Br J Cancer 77:855-61
Grayhack, J T; Sensibar, J A; Ilio, K Y et al. (1998) Synergistic action of steroids and spermatocele fluid on in vitro proliferation of prostate stroma. J Urol 159:2202-9
Gann, P H; Chatterton, R; Vogelsong, K et al. (1997) Epidermal growth factor-related peptides in human prostatic fluid: sources of variability in assay results. Prostate 32:234-40

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