Functional role of DNA mismatch repair gene PMS2 in prostate cancer cells
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Shinichiro Fukuhara1,2,3,*, Inik Chang1,4,*, Yozo Mitsui1,2,5, Takeshi Chiyomaru1,2,6, Soichiro Yamamura1,2, Shahana Majid1,2, Sharanjot Saini1,2, Guoren Deng1,2, Ankurpreet Gill1, Darryn K. Wong1, Hiroaki Shiina5, Norio Nonomura3, Yun-Fai C. Lau7,8, Rajvir Dahiya1,2, Yuichiro Tanaka1,2
1Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America
2Department of Urology, University of California, San Francisco, California 94121, United States of America
3Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
4Department of Oral Biology, Yonsei University College of Dentistry, Seoul 120-752, South Korea
5Department of Urology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan
6Department of Urology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
7Department of Medicine, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America
8Institute for Human Genetics, University of California, San Francisco, California 94121, United States of America
*These authors have contributed equally to this work
Yuichiro Tanaka, e-mail: [email protected]
Keywords: PMS2, apoptosis, prostate cancer
Received: January 02, 2015 Accepted: April 24, 2015 Published: May 06, 2015
DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintains genomic integrity and MMR-deficient cells show an increased mutation rate. MMR has also been shown to influence cell signaling and the regulation of tumor development. MMR consists of various genes and includes post-meiotic segregation (PMS) 2 which is a vital component of mutL-alpha. In prostate, the functional role of this gene has never been reported and in this study, our aim was to investigate the effect of PMS2 on growth properties of prostate cancer (PCa) cells. Previous studies have shown PMS2 to be deficient in DU145 cells and this lack of expression was confirmed by Western blotting whereas normal prostatic PWR-1E and RWPE-1 cells expressed this gene. PMS2 effects on various growth properties of DU145 were then determined by creating stable gene transfectants. Interestingly, PMS2 caused decreased cell proliferation, migration, invasion, and in vivo growth; and increased apoptosis as compared to vector control. We further analyzed genes affected by PMS2 expression and observe the apoptosis-related TMS1 gene to be significantly upregulated whereas anti-apoptotic BCL2A1 was downregulated. These results demonstrate a functional role for PMS2 to protect against PCa progression by enhancing apoptosis of PCa cells.
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