Keratinocyte growth factor in the rat ventral prostate: androgen-independent expression

Abstract

Keratinocyte growth factor (KGF/FGF-7) is a stromally derived factor which exerts proliferative and differentiating effects on a variety of epithelial cells. Results of recent studies utilizing in vitro methods such as tissue culture and organ culture have suggested that KGF may act as a paracrine mediator of androgen-induced growth and development of the prostate and seminal vesicle. We undertook the present study to determine the distribution of KGF in relation to the functional regions of the rat prostatic ductal system, and whether KGF expression is influenced by androgen in vivo. Immunohistochemical staining revealed KGF to be present in the stroma throughout the prostate, regardless of the functional region, and staining for KGF remained high through 21 days post-castration. Message for KGF could also be detected by reverse transcriptase-PCR analysis of prostate stromal cells isolated from 4-and 21-day castrated animals, and no gross change in message level was observed following castration. Furthermore, no significant change in either stromal staining or message for KGF was observed in newborn rat prostates 10 days after castration, suggesting a similar regulatory mechanism for KGF in the adult and immature prostate. Epithelial staining for KGF decreased following castration, and greatly increased upon androgen replacement, possibly indicating a change in KGF internalization. These observations suggest that the presence of KGF protein is not related to functional differences in the prostate epithelium, and that expression of KGF in vivo is not greatly influenced by androgen.

Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo

“…In addition, expression of IGF-I mRNA in benign human prostatic stroma was significantly decreased after surgical castration therapy (Ohlson et al 2007). In contrast to FGF-2 and IGF-I, expression of FGF-7 mRNA in rat prostate was not significantly influenced by castration (Nemeth et al 1998). Therefore, androgen-independent expression of certain stromal growth factors such as FGF-7 could be given consideration as a concept to treat hormone-refractory PCa in combination with androgen ablation.…”

Influence of stromal–epithelial interactions on androgen action

“…For example, it was suggested that AR could mediate the upregulation of FGF7 (Yan et al 1992, Nemeth et al 1998, Planz et al 1998, Giri & Ittmann 2000. This would be important in the context of prostate cancer because embryology studies have shown that FGF7 is a potent stimulator of epithelial growth and may assist androgens in early prostate growth (Hom et al 1998).…”

The role of fibroblast growth factors and their receptors in prostate cancer

“…FGF7 is present at approximately 28 ng/g wet weight in normal prostate (Giri et al 1999a and is actively secreted. It has been reported that FGF7 is induced by androgens in cultures of rat (Yan et al 1992) and human (Planz et al 1998) prostatic stromal cells, but observations on castrated rats indicated that FGF7 expression in the prostate may not be androgen regulated in vivo (Nemeth et al 1998) so the effect of androgens on FGF7 production is controversial. Our laboratory has shown a small increase in FGF7 secretion in organ cultures of normal prostate tissue in response to androgens (authors' unpublished data), supporting the idea that FGF7 expression by stromal cells can be regulated at least partially by androgens, but other factors may be more important (Giri & Ittmann 2000).…”