Abstract A160: Regulation of resistance of prostate cancer cells to chemotherapy by nanog, a transcription factor for self-renewal of stem cells

Abstract

Abstract Nanog is a transcription factor usually expressed in embryonic stem cells that plays essential role in the stem cell self-renewal. Expression of Nanog has been detected in a number of cancer cells, especially in those positive for stem/progenitor markers. In the present studies, it was found that there was elevated expression of Nanog in the surviving fractions of tumor cells after chemotherapy. Prospective enrichment of tumor cells with endogenous Nanog expression led to enrichment of tumor cells resistant to Taxol, vinblastine, and doxorubicin, but not camptothecin (CPT). The increased resistance in Nanog expressing cells was attenuated, but not abolished, by inhibitors of p-glycoprotein, the ATP-bind cassette efflux transporter B1 (ABCB1), or by knockdown of ABCB1 via small hairpin RNAs (shRNAs). Expression of ABCB1 was increased in tumor cells enriched with endogenous Nanog expression while knockdown of Nanog reduced the expression of ABCB1 and sensitized tumor cells toward chemotherapeutics. Together, our results suggest that Nanog confers tumor cells with increased resistance to chemotherapy via regulating the expression of ABC transporters. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A160.