Ethnic differences in TGFβ-signaling pathway may contribute to prostate cancer health disparity

Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared with Caucasian (CA) men in the United States. Transforming growth factor beta (TGF beta) signaling pathway is linked to health disparities in AAs. Recent studies suggest a role of TGF beta 3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in PCa in AA men has not been studied. We determined the circulating levels of TGF beta 3 in AA and CA men diagnosed with PCa using ELISA. We analyzed serum samples from both AA and CA men diagnosed with and without PCa. We show that AA PCa patients had higher levels of TGF beta 3 protein compared with AA controls and CA patients. In fact, TGF beta 3 protein levels in serum were higher in AA men without PCa compared with the CA population, which may correlate with more aggressive disease seen in AA men. Studies on AA-derived PCa cell lines revealed that TGF beta 3 protein levels were also higher in these cells compared with CA-derived PCa cell lines. Our studies also reveal that TGF beta does not inhibit cell proliferation in AA-derived PCa cell lines, but it does induce migration and invasion through activation of PI3K pathway. We suggest that increased TGF beta 3 levels are responsible for development of aggressive PCa in AA patients as a consequence of development of resistance to inhibitory effects of TGF beta on cell proliferation and induction of invasive metastatic behavior.