title: Benign prostatic stromal cells are regulated by basic fibroblast growth factor and transforming growth factor-beta 1.
abstract: The current study was undertaken, using cultures of prostatic epithelial and stromal cells, to determine the functional interactions between androgens, basic fibroblast growth factor (FGF2) and transforming growth factor-beta 1 (TGF beta 1) and their importance in maintaining stromal homeostasis. Treatment of stromal cells with TGF beta 1 significantly increased intracellular FGF2 and FGF2 sequestered to the extracellular matrix. FGF2 was also detected in stromal conditioned medium (SCM), but at levels 70-fold less than found in cell lysates. TGF beta 1 (0.1 ng/ml) treatment caused an initial increase of 86% in secreted FGF2 levels, but high concentrations of TGF beta 1 (5 ng/ml) decreased FGF2 levels by 38%, relative to the untreated control. Further studies showed that epithelial conditioned medium (ECM), androgen-treated, stromal conditioned medium (ASCM), but not SCM were mitogenic for stromal cells. Both ECM and ASCM caused a threefold increase in DNA synthesis. FGF2 may be the mediator of these interactions, since the mitogenic effect of both ECM and ASCM was significantly reduced by the addition of anti-FGF2 neutralising antibody. We hypothesise that the lack of response of stromal cells to SCM is due to TGF beta 1 blocking the mitogenic effect of FGF2. Thus down-regulation of TGF beta 1 synthesis, by androgens, results in stromal proliferation by ASCM.
authors.affiliation: Department of Surgery, The Medical School, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Collins
authors.forename: E J
authors.initials: EJ
authors.lastname: Robinson
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D045165:Testosterone Congeners / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D045165:Testosterone Congeners; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D009277:Nandrolone; D004247:DNA; C100075:mibolerone