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Functional role of DNA mismatch repair gene PMS2 in prostate cancer cells.

 Shinichiro Fukuhara  ;  Inik Chang  ;  Yozo Mitsui  ;  Takeshi Chiyomaru  ;  Soichiro Yamamura  ;  Shahana Majid  ;  Sharanjot Saini  ;  Guoren Deng  ;  Ankurpreet Gill  ;  Darryn K. Wong  ;  Hiroaki Shiina  ;  Norio Nonomura  ;  Yun-Fai C. Lau  ;  Rajvir Dahiya  ;  Yuichiro Tanaka 
 ONCOTARGET , Vol.6(18) : 16341-16351, 2015 
Journal Title
Issue Date
Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism* ; Apoptosis/genetics* ; CARD Signaling Adaptor Proteins ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cytoskeletal Proteins/biosynthesis ; DNA/genetics ; DNA Mismatch Repair/genetics* ; DNA Repair Enzymes/genetics ; DNA Repair Enzymes/metabolism* ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism* ; Humans ; Male ; Minor Histocompatibility Antigens ; Mismatch Repair Endonuclease PMS2 ; Neoplasm Invasiveness/genetics ; Prostate ; Prostatic Neoplasms/genetics* ; Prostatic Neoplasms/pathology* ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; RNA Interference ; RNA, Small Interfering
PMS2 ; apoptosis ; prostate cancer
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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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
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