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.