title: Functional role of DNA mismatch repair gene PMS2 in prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.|Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Oral Biology, Yonsei University College of Dentistry, Seoul 120-752, South Korea.
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.|Department of Urology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.|Department of Urology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.
authors.forename: Ankurpreet
authors.initials: A
authors.lastname: Gill
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.
authors.forename: Darryn K
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Institute for Human Genetics, University of California, San Francisco, California 94121, United States of America.
authors.forename: Yun-Fai C
authors.initials: YF
authors.lastname: Lau
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
authors.affiliation: Department of Surgery/Urology, Veterans Affairs Medical Center, San Francisco, California 94121, United States of America.|Department of Urology, University of California, San Francisco, California 94121, United States of America.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004247:DNA / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D000070976:Mismatch Repair Endonuclease PMS2; D009361:Neoplasm Invasiveness / Q000235:genetics; D011467:Prostate; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C096816:BCL2-related protein A1; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C402202:PYCARD protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D004247:DNA; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes
keywords: PMS2; apoptosis; prostate cancer