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 angiogenesis, and inhibit apoptosis, all of which play an important role in
tumor progression. To determine whether FGFs are overexpressed in human
prostate cancers, we analyzed 26
prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal prostate tissue by this technique. Fourteen of 26
prostate cancers expressed FGF6
mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of
tissue extracts of normal prostate, high-grade
prostatic intraepithelial neoplasia (PIN), and
prostate cancer for FGF6 showed that this
growth factor was undetectable 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 normal 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 cells. 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 vivo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN and
prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms.