BCO2 Inhibits NF-{kappa}B Signaling in Prostate Cancer

This study investigated expression and functional roles of BCO2 in human prostate cancer. Expression of the bco2 gene is dramatically decreased in prostate cancer tissue and in a range of prostate cancer cell lines as compared with nonneoplastic prostate tissue and normal prostatic epithelial cells, respectively. Inhibition of DNA methyltransferase activity restored bco2 expression in prostate cancer cell lines tested. Treatment with lycopene or its metabolite, apo-10-lycopenal, also increased bco2 expression and reduced cell proliferation in androgen-sensitive cell lines, but lycopene neither altered bco2 expression nor cell growth in androgen-resistant cells. Notably, restoring bco2 expression in prostate cancer cells inhibited cell proliferation and colony formation, irrespective of lycopene exposure. Exogenous expression of either wild-type BCO2 or a mutant (enzymatically inactive) BCO2 in prostate cancer cells reduced NF-B activity and decreased NF-B nuclear translocation and DNA binding. Together, these results indicate epigenetic loss of BCO2 expression is associated with prostate cancer progression. Moreover, these findings describe previously unanticipated functions of BCO2 that are independent of its enzymatic role in lycopene metabolism. Implications: This study identifies BCO2 as a tumor suppressor in prostate cancer. BCO2-mediated inhibition of NF-B signaling implies BCO2 status is important in prostate cancer progression. Mol Cancer Res; 14(10); 966–75. &c...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Oncogenes and Tumor Suppressors Source Type: research