Three fibroblast growth factors (FGFs), acidic FGF (FGF1), basic FGF (FGF2), and keratinocyte growth factor (FGF7) have been identified in prostate. To understand how FGFs regulate growth of the prostate, and to determine if regulation is altered in benign prostatic hyperplasia (BPH), the mitogenic potential of FGFs, receptor binding, and FGF-receptor (FGFR) gene expression of stromal (PS) and epithelial cells (PE) cultured from normal human prostate and BPH where determined. FGF1 and FGF2, but not FGF7, were mitogens for PS. FGF1 and FGF7 were potent mitogens for PE, but FGF2 was a weak mitogen for these cells. Both PS and PE exhibited high affinity binding (pM K) of iodinated-FGF2. The K was 4-fold and 12-fold higher for PS than for PE cultured from normal prostate and BPH, respectively. Northern analysis indicated that PS, but not PE, expressed FGFR type 1 (FGFR1) mRNA. The reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate FGFR type 2 (FGFR2) expression. The size of amplified DNA fragments, and nucleotide sequences, indicated that PS also expressed transcripts for the exon IIIc RNA splice variant of FGFR2. A RT-PCR product with the FGFR2 exon IIIb nucleotide sequence joined with the exon IIIc sequence was amplified with poly A+ RNA from PE and primers spanning both exons. Thus, PE did not alternatively splice mRNA for FGFR2 exon IIIb and exon IIIc. No differences in the mitogenic potential of FGFs, receptor binding (K or number of sites), or FGFR gene expression were found in cells cultured from normal prostate and BPH.

Transforming growth factor beta s (TGF beta s) are members of a superfamily of polypeptides that control cell cycle progression and a variety of other cellular activities. TGF beta family members, -beta 1, -beta 2, and -beta 3, have been identified in prostate. The levels of expression of these TGF beta isotypes have been reported to vary with the pathologic state of the prostate. While the significance of these observations remains to be elucidated there is little doubt that TGF beta s play an important role in controlling growth of the prostate. The prostatic cells expressing TGF beta s have not been identified. This information would provide insight into the physiologic role of TGF beta s and suggest ways that growth control may be altered in prostate disease. We used stromal (PS) and epithelial (PE) cells, cultured from normal human prostate and benign prostatic hyperplasia (BPH), to study the effect of TGF beta s on cell proliferation and TGF beta transcript and protein expression. The proliferation of PS and PE was inhibited by pM quantities of TGF beta 1, -beta 2, and -beta 3. Both cell types expressed transcripts for all three TGF beta isotypes, but PS primarily secreted TGF beta 1, whereas PE secreted more TGF beta 2 than TGF beta 1. These observations suggest that TGF beta s are antiproliferative agents in vivo, and that the stroma is the source of TGF beta 1 while the epithelium is the major source of TGF beta 2 in prostate. There were no significant differences in the growth response to TGF beta s, the TGF beta-isotype expressed, or the amount of TGF beta secreted by cells cultured from normal prostate or BPH.

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