Abstract
Abstract NANOG promotes chemoresistance in prostate carcinoma cells Hongmei Jiang, Man-Tzu Wang, Daotai Nie The emergence of drug resistant prostate cancer cells is a leading cause of chemotherapy failure in patients with prostate cancer. The mechanisms behind the acquisition of chemoresistance in prostate cancers are, however, poorly understood. NANOG is a transcription factor associated with the self-renewal of embryonic stem cells. Expression of NANOG has been detected in a number of cancer cells, and its expression linked with those positive for stem/progenitor markers. In the present studies, several lines of evidence are presented to suggest that NANOG regulates tumor responses to chemotherapy. First, in the surviving fractions of tumor cells after chemotherapy, there was an elevated level of NANOG expression and activities. Second, prospective enrichment of tumor cells with endogenous NANOG expression led to enrichment of tumor cells resistant to taxol, vinblastine, and doxorubicin. Knockdown of NANOG expression via small hairpin RNAs (shRNAs) sensitized tumor cells toward chemotherapeutics. Real-time PCR array identified an enhanced expression of the ATP-binding cassette efflux transporter B1 (ABCB1) and G2 (ABCG2) in tumor cells enriched with endogenous NANOG expression. Inhibition of ABCB1 activities or knockdown of ABCB1 expression attenuated, but not abolished, the increased resistance in NANOG expressing cells toward taxol and vinblastine. Knockdown of ABCG2 attenuated the resistance of NANOG-expressing tumor cells toward doxorubicin. Together, our results suggest that NANOG confers tumor cells with increased resistance to chemotherapy partially through regulating the expression of ABC transporters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-292. doi:1538-7445.AM2012-LB-292
Published Version
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