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Elliott B, Zackery DL, Eaton VA, Jones RT, Abebe F, Ragin CC, Khan SA
Ethnic Differences in TGFbeta Signaling Pathway May Contribute to Prostate Cancer Health Disparity
Carcinogenesis (2018) 39:546-555.
Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared to Caucasian (CA) men in the US. Transforming growth factor beta (TGFbeta) signaling pathway is linked to health disparities in African-Americans. Recent studies suggest a role of TGFbeta3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in prostate cancer in African American men has not been studied. We determined the circulating levels of TGFbeta3 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 prostate cancer patients had higher levels of TGFbeta3 protein compared to AA controls and CA patients. In fact, TGFbeta3 protein levels in serum were higher in AA men without PCa compared to the CA population, which may correlate with more aggressive disease seen in AA men. Studies on AA derived PCa cell lines revealed that TGFbeta3 protein levels were also higher in these cells compared to CA derived PCa cell lines. Our studies also reveal that TGFbeta 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 TGFbeta3 levels are responsible for development of aggressive prostate cancer in AA patients as a consequence of development of resistance to inhibitory effects of TGFbeta on cell proliferation and induction of invasive metastatic behavior.
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Publication Date: 2018-04-05.
PMCID: PMC5889036
Last updated on Friday, July 10, 2020