Approximately 350,000 prostatectomies are performed each year to relieve the symptoms of urinary-outlet obstruction of benign prostatic hyperplasia (BPH); resulting in medical expenses that well exceed $1 billion per year in the United States. Despite efforts to seek the cause of this disorder the only factors that have been consistently associated with this disease are the presence of the testes and aging. Our findings that BPH tissue contains basic fibroblast growth factor (bFGF), a mitogen for mesodermal cells including prostatic fibroblasts, suggests that the growth factor may be important in the development of fibrostromal nodules characteristic of human BPH. This proposal seeks support to 1) develop new antibody to bFGF to increase the sensitivity and specificity of existing assays for the growth factor. 2) To determine the distribution of bFGF in normal prostate and BPH. Thus, testing the hypothesis that bFGF is elevated in regions of the prostate where BPH is thought to arise. 3) To determine if bFGF is synthesized by prostatic stromal and/or epithelial cells in culture. These studies will differentiate between an autocrine or paracrine regulatory role for bFGF. 4) To determine if androgen influences bFGF synthesis or availability to cells with growth factor receptor. 5) To identify the prostatic cell population with bFGF receptor and to determine if receptor binding and number is the same in cells from the normal prostate and BPH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK031063-07
Application #
3229835
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1982-01-01
Project End
1992-06-30
Budget Start
1988-08-01
Budget End
1989-06-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Story, M T; Hopp, K A; Meier, D A (1996) Regulation of basic fibroblast growth factor expression by transforming growth factor beta in cultured human prostate stromal cells. Prostate 28:219-26
Story, M T; Hopp, K A; Molter, M (1996) Expression of transforming growth factor beta 1 (TGF beta 1), -beta 2, and- beta 3 by cultured human prostate cells. J Cell Physiol 169:97-107
Begun, F P; Story, M T; Hopp, K A et al. (1995) Regional concentration of basic fibroblast growth factor in normal and benign hyperplastic human prostates. J Urol 153:839-43
Story, M T (1995) Regulation of prostate growth by fibroblast growth factors. World J Urol 13:297-305
Story, M T; Hopp, K A; Molter, M et al. (1994) Characteristics of FGF-receptors expressed by stromal and epithelial cells cultured from normal and hyperplastic prostates. Growth Factors 10:269-80
Story, M T; Hopp, K A; Meier, D A et al. (1993) Influence of transforming growth factor beta 1 and other growth factors on basic fibroblast growth factor level and proliferation of cultured human prostate-derived fibroblasts. Prostate 22:183-97
Story, M T (1991) Polypeptide modulators of prostatic growth and development. Cancer Surv 11:123-46
Story, M T; Livingston, B; Baeten, L et al. (1989) Cultured human prostate-derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor. Prostate 15:355-65
Story, M T (1989) Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor. In Vitro Cell Dev Biol 25:402-8