title: Artemin Reduces Sensitivity to Doxorubicin and Paclitaxel in Endometrial Carcinoma Cells through Specific Regulation of CD24.
abstract: We have previously reported that artemin (ARTN) stimulates the oncogenicity and invasiveness of endometrial carcinoma cells. Herein, we demonstrate that ARTN modulates the sensitivity of endometrial carcinoma cells to agents used to treat late-stage endometrial carcinoma. Forced expression of ARTN in endometrial carcinoma cells decreased sensitivity to doxorubicin and paclitaxel. Accordingly, depletion of ARTN by small interfering RNA or functional inhibition of ARTN with antibodies significantly increased sensitivity of endometrial carcinoma cells to doxorubicin and paclitaxel. Forced expression of ARTN in endometrial carcinoma cells abrogated doxorubicin-induced G(2)-M arrest and paclitaxel-induced apoptosis. ARTN increased CD24 expression in endometrial carcinoma cells by transcriptional up-regulation, and CD24 was partially correlated to ARTN expression in endometrial carcinoma. Forced expression of CD24 in endometrial carcinoma cells stimulated cell proliferation and oncogenicity, enhanced cell invasion, and decreased sensitivity to doxorubicin and paclitaxel. Depletion of CD24 in endometrial carcinoma cells abrogated ARTN-stimulated resistance to doxorubicin and paclitaxel. ARTN-stimulated resistance to doxorubicin and paclitaxel in endometrial carcinoma cells is therefore mediated by the specific regulation of CD24. Functional inhibition of ARTN may therefore be considered as an adjuvant therapeutic approach to improve the response of endometrial carcinoma to specific chemotherapeutic agents.
authors.affiliation: The Liggins Institute, Auckland, University of Auckland, Auckland, New Zealand.
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.forename: Yewon
authors.initials: Y
authors.lastname: Jung
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Michael
authors.initials: M
authors.lastname: Steiner
authors.forename: Peng-Xu
authors.initials: PX
authors.lastname: Qian
authors.forename: Arindam
authors.initials: A
authors.lastname: Banerjee
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie