Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer

Fibroblast growth factors (FGFs) are known to play an important role in the growth of normal prostatic epithelial cells. In addition to their effects on proliferation, FGFs can promote cell motility, increase tumor angiogenes is, and inhibit apoptosis, all of which play an important role in tumor pro gression. To determine whether FGFs are overexpressed in human prostate can cers, we analyzed 26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal pros tate tissue by this technique. Fourteen of 26 prostate cancers expressed FG F6 mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of tissue ext racts of normal prostate, high-grade prostatic intraepithelial neoplasia (P IN), and prostate cancer for FGF6 showed that this growth factor was undete ctable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak staining of prostatic basal cells in norm al prostate that was markedly elevated in PIN. In the prostate cancers, the majority of cases revealed expression of FGF6 by the prostate cancer cells themselves. In two cases, expression was present in prostatic stromal cell s. Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vi vo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN an d prostate cancer and can promote the proliferation of the transformed pros tatic epithelial cells via paracrine and autocrine mechanisms.