Down-regulation of MSH2 expression by Hsp90 inhibition enhances cytotoxicity affected by tamoxifen in human lung cancer cells》.pdf

Biochemical and Biophysical Research Communications 456 (2015) 506–512 Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.else /loc ate/ybbrc Down-regulation of MSH2 expression by Hsp90 inhibition enhances cytotoxicity affected by tamoxifen in human lung cancer cells Jen-Chung Ko a, Hsien-Chun Chiu b, Jhan-Jhang Syu b, Chien-Yu Chen b, Yun-Ting Jian b, Yi-Jhen Huang b, Ting-Yu Wo b, Yi-Jun Jian b, Po-Yuan Chang b, Tai-Jing Wang b, Yun-Wei Lin b,⇑ a Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan b Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan a r t i c l e i n f o a b s t r a c t Article history: The anti-estrogen tamoxifen has been used worldwide as an adjuvant hormone therapeutic agent in the Received 20 November 2014 treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in Available online 6 December 2014 non-small cell lung cancer (NSCLC) cells has not been identified. Human MutS homolog 2 (MSH2), a crucial element of the highly conserved DNA mismatch repair system, and expression of MSH2 have been Keywords: down-regulated by Hsp90 function inhibition in human lung cancer. Therefore, in this study, we exam- MSH2 ined whether MSH2 plays a role in the tamoxifen and Hsp90 inhibitor-induced cytotoxic effect on NSCLC AKT cells. The results showed that treatment with tamoxifen increased MS