Abstract 1756: Downregulation of topoisomerase IIα by all-trans retinoic acid in human cervical carcinoma cells

Abstract

Abstract Cervical cancer remains a threatening disease to women worldwide. Topoisomerase IIα is a novel proliferation marker for cervical cancer diagnosis, therapy and prognosis. Understanding of the regulation of topoisomerase IIα would facilitate prevention and therapy of cervical cancer. In the present study, a significant repression of topoisomerase IIα level in stage Ib of squamous cervical carcinoma tissue was observed in patients with chemotherapeutic treatment, suggesting topoisomerase IIα is a target for chemotherapeutic drugs. All-trans-retinoic acid (ATRA), a chemopreventive agent, was shown to suppress both endogenous and exogenous topoisomerase IIα protein but not mRNA expression in human cervical carcinoma HeLa cells. Cycloheximide (CHX) prior to ATRA treatment augmented the topoisomerase IIα instability. ATRA induced the degradation of topoisomerase IIα via the proteasome pathway but not lysosome pathway. Ubiquitination was involved in this ATRA-induced topoisomerase IIα degradation. The ATRA-induced topoisomerase IIα repression occurred only in cell nucleus. Interestingly, overexpression of topoisomerase IIα enhanced cyclin D1 expression and caused HeLa cells de-differentiation while knockdown of topoisomerase IIα resulted in the cells differentiation and decreased cyclin D1. ATRA suppressed drug resistant protein P-gp while the typical topoisomerase II inhibitor etoposide did not. The molecular therapeutic implication of ATRA in cervical cancer therapy is discussed. 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 1756. doi:1538-7445.AM2012-1756