Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

摘要

Prostate cancer cells express multiple types of FGF receptor and increased expression of FGF receptor-I (FGFR-I) is present in poorly differentiated human prostate cancers in vivo. We have proposed to evaluate biological affects of DN FGFR expression in human primary prostate epithelial cells and prostate cancer cell lines. The findings in this report support that prostate cancer cells are dependent upon FGFR signaling for survival and cells treated with DN FGFR are arrested G2/M phase of cell cycle followed by cell death. FGF signaling modulated CDC25C activity in prostate cancer and in this manner can promote progression through the G2/M checkpoint. CDC25C protein is upregulated in comparison to normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Determining other molecules involved in this pathway contributing tumor growth and survival will facilitate the development of cancer therapies to target FGF signaling pathway.