Abstract 1238: Effects of MLH1 on prostate cancer cell function

Abstract

Abstract Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer. MMR can influence the regulation of tumor development in various cancers but their role on prostate cancer has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of prostate cancer cells. The DU145 prostate cancer cell line has been previously established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal prostatic PWR-1E and RWPE-1 cells. Stably expressing MLH1 in DU145 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth using athymic nude mice model also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with imatinib (STI571) also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against prostate cancer development by inducing c-Abl-mediated apoptosis. Citation Format: Shinichiro Fukuhara, Inik Chang, Yozo Mitsui, Soichiro Yamamura, Takeshi Chiyomaru, Shahana Majid, Sharanjot Saini, Hiroshi Hirata, Guoren Deng, Ankurpreet Gill, Darryn K. Wong, Hiroaki Shiina, Norio Nonomura, Rajvir Dahiya, Yuichiro Tanaka. Effects of MLH1 on prostate cancer cell function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1238. doi:10.1158/1538-7445.AM2015-1238