Activation of FGF2-FGFR signaling in the castrated mouse prostate stimulates the proliferation of basal epithelial cells.
The prostate gland is unique in that it undergoes rapid regression following castration but regenerates completely once androgens are replaced. Residual ductal components play an important role in the regeneration of a fully functional prostate. In this study, to examine how androgen status affects prostate structure and components, we conducted histopathological studies of the involuted and regenerated mouse dorsolateral prostate (DLP). In the castrated mouse DLP, the number of luminal epithelial cells decreased in a time-dependent manner. On Day 14 postandrogen replacement, the number of luminal epithelial cells was completely restored to the baseline level. In contrast, the number of basal epithelial cells gradually increased in the castrated mouse prostate. The Ki67-labeling index of prostate basal epithelial cells was significantly increased after castration. The number of basal epithelial cells decreased to baseline after androgen replacement. After castration, mRNA expression levels of specific growth factors, such as Fgf2, Fgf7, Hgf, Tgfa, and Tgfb, were relatively abundant in whole mouse DLPs. In organ culture experiments, basal epithelial proliferation was recapitulated in the absence of dihydrotestosterone (DHT). The proliferation of basal epithelial cells in the absence of DHT was suppressed by treatment with an FGF receptor inhibitor (PD173074). Moreover, FGF2 treatment directly stimulated the proliferation of basal epithelial cells. Taken together, these data indicated that the FGF2-FGF receptor signal cascade in the prostate gland may be one of the pathways stimulating the proliferation of basal epithelial cells in the absence of androgens.
Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Manabu
M
Kato
Kenichiro
K
Ishii
Yoichi
Y
Iwamoto
Takeshi
T
Sasaki
Hideki
H
Kanda
Yasushi
Y
Yamada
Kiminobu
K
Arima
Taizo
T
Shiraishi
Yoshiki
Y
Sugimura
D000728:Androgens / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002369:Castration / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020249:Hormone Replacement Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015291:Transforming Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000728:Androgens; C496454:Fgf7 protein, mouse; C553307:HGF protein, mouse; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D017228:Hepatocyte Growth Factor; D015291:Transforming Growth Factors; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
basal epithelial cells; castration; fibroblast growth factor 2; fibroblast growth factor receptor; growth factor; organ culture; prostate