Androgen-stimulated human prostate epithelial growth mediated by stromal-derived fibroblast growth factor-10.
It has been suggested that prostate homeostasis is regulated indirectly by androgens through stromal-epithelial interactions in part by factors from the stromal cells acting on receptors in epithelial cells. In this report, the role of fibroblast growth factor (FGF)-10 in prostatic epithelial proliferation was investigated. The expression of FGF-10 mRNA was apparent in primary-cultured stromal cells, but not in epithelial cells derived from human tissue from patients with benign prostatic hyperplasia (BPH). The mitogenic activity of human recombinant FGF-10 assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation was demonstrated in isolated epithelial cells, but not in cultured stromal cells. No mitogenic activity of dihydrotestosterone (DHT) for either epithelial or stromal cells could be demonstrated, but quantitative PCR (real-time PCR) with a double-labeled fluorogenic probe demonstrated that expression of FGF-10 in stromal cells was enhanced 5.3-fold at a DHT concentration of 100 pM. Androgen receptor mRNA levels showed no significant change with DHT at concentrations less than 100 pM, but were reduced to 50% of control levels at a DHT concentration of 10 nM. These results suggest that stromal-derived FGF-10 stimulates human prostatic epithelial growth and its mRNA expression is induced by androgens, without an increase in the androgen receptor mRNA. Moreover, FGF-10 may be involved in the development or support of human BPH.
Nakano
K
K
Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Fukabori
Y
Y
Itoh
N
N
Lu
W
W
Kan
M
M
McKeehan
W L
WL
Yamanaka
H
H
D000728:Androgens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology*; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism*
D000728:Androgens; C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; D005346:Fibroblast Growth Factors