The etiology of human BPH pathogenesis, although remains unclear, ar centered around testes, aging, and morphological and functional changes within the prostate. The present study seeks to identify and characterize the morphological and functional changes that develop in BPH. Use of newly developed techniques such as 2-D electrophoresis and immunocytochemistry for cytoskeleton proteins should provide new insight into local changes that characterize BPH. Since the prostate epithelial cells are a group of highly differentiated and specialized cells, changes in pathological states of the tissue are likely associated with changes in expression of PAP and PSA. Therefore the present application proposes to investigate morphological and functional changes within the prostate that are associated with BPH. We propose to examine human prostate surgical specimens and human prostate secretions. The prostatic specimens will include the normal prostate, carcinoma of the prostate, and BPH, especially, the edenoma and the peripheral tissues of the same prostate. The following studies are proposed: (1) To study the cellular localization and distribution of cytoskeletal proteins: microtubules, microfilaments and intermediate filaments and their associated proteins in various cell types of human prostatic tissues, (2) To conduct 2-D electrophoresis on different human prostatic tissues and to identify different cytoskeletal proteins in this 2-D protein profile using Western Blot technique, (3) By comparison of the results of the above two studies, proteins associated with specific cell types will be identified and further purified. Specific antibodies can be developed from these purified proteins as probes for further investigation and for possible use in clinical diagnosis (4) Biochemical and immunohistochemical analysis of prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) in different human prostatic tissues. In addition, total tissue DNA and total protein content in these tissues will be analyzed. Special attention will be given to investigate and differences between the adenoma and the peripheral prostate tissue of the same prostate gland with BPH. (5) Since prostatic fluid composition may reflect metabolic and pathologic state of the prostate cells, the following study is also proposed: Characterization of proteins in prostatic fluid from men with """"""""normal"""""""" prostate, carcinoma of the prostate, and BPH by 2-D electrophoresis.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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
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
Lee, C; Sintich, S M; Mathews, E P et al. (1999) Transforming growth factor-beta in benign and malignant prostate. Prostate 39:285-90
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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