Opposing actions of TGFbeta1 and FGF2 on growth, differentiation and extracellular matrix accumulation in prostatic stromal cells.
TGFbeta 1 and FGF2 are autocrine growth factors in prostatic stroma and are elevated in benign prostatic hyperplasia (BPH), a disease characterized by enlargement of the stromal compartment of the prostate. TGFbeta1 has a biphasic effect on proliferation of prostatic stromal cells, inducing proliferation at low doses (< 1 ng/ml), but inhibiting growth above 1 ng/ml. This study investigated the role of TGFP 1 and FGF2 on growth factor bioavailability and extracellular matrix (ECM) accumulation synthesis in cultured prostatic stromal cells. Real-Time-PCR showed that TGFbeta1 expression is auto-inductive, whereas FGF2 is auto-repressive. FGF2 also induced TGFbeta1 secretion in the absence of increased TGFbeta1 mRNA expression. TGFbeta1 and FGF2 have opposing actions on Type 1 collagen expression, a finding confirmed by Western blotting. The bioavailability of TGFbeta1 regulated by FGF2 may represent part of a negative feedback mechanism controlling stromal growth, differentiation and ECM. Dysregulation of this pathway in favour of TGFbeta1 bioactivity may exacerbate BPH.
Cross
Neil A
NA
Academic Unit of Urology, University of Sheffield Medical School, Sheffield, UK. n.a.cross@shef.ac.uk
Reid
Sheilagh V
SV
Harvey
Amanda J
AJ
Jokonya
Nickie
N
Eaton
Colby L
CL
D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D011467:Prostate / Q000166:cytology / Q000187:drug effects*; D011470:Prostatic Hyperplasia; D017154:Stromal Cells / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2