Abstract Prostate cancer is one of the most common malignancies and ranks the second most common cause of cancer-related deaths in men. DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. Recent studies have shown that MMR influences the regulation of tumor development in various cancers such as colon, ovarian and others, but their effect on prostate cancer growth has not been investigated thus far. The aim of the present study was to investigate the effect of the post-meiotic segregation (PMS) 2 MMR gene on growth properties of prostate cancer cells. Expression of PMS2 was initially measured in normal and cancerous prostate cell lines by real-time PCR and western blotting. Cancerous cells displaying the lowest levels compared to normal cells was then transfected with PMS2. Gene effect on various cellular properties (cell proliferation, migration, invasion, apoptosis and cell cycle assays) as well as growth in nude mice were determined. Of the various prostate cell lines, DU145 had dramatically reduced expression levels of PMS2 with little protein detected, whereas levels were high in normal prostate cells. Interestingly, over-expressing the PMS2 gene in DU145 cells decreased cell proliferation, migration and invasion, and increased apoptosis and cell cycle arrest compared to vector control. PMS2 also inhibited DU145 cell tumor formation in animal models. These results demonstrate PMS2 to protect against prostate cancer progression and to have a functional role by affecting apoptosis and cell cycle of prostate cancer cells. Citation Format: Shinichiro Fukuhara, Inik Chang, varahram shahryari, ankurpreet gill, darryn K. wong, soichiro yamamura, shahana majid, sharanjot saini, hiroshi hirata, koji ueno, gouren deng, laura Z. tabatabai, norio nonomura, rajvir dahiya, yuichiro tanaka. DNA mismatch repair protein, PMS2, induces apoptosis in human prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2424. doi:10.1158/1538-7445.AM2014-2424