title: MDH2 Stimulated by Estrogen-GPR30 Pathway Down-Regulated PTEN Expression Promoting the Proliferation and Invasion of Cells in Endometrial Cancer.
abstract: OBJECTIVE
  The relationship between endometrial carcinoma and cellular metabolism is unknown. In endometrial cancer, mutation rate of PTEN has been reported very high. Malate dehydrogenase 2 (MDH2) is one of the isoforms of malate dehydrogenase, which is involved in citric acid cycle in mitochondria. Our study aimed to investigate the role MDH2 played in PTEN-regulated endometrial carcinoma.
  
  
  METHODS
  To reveal the expression of MDH2 and the co-localization of PTEN and MDH2, immunohistochemistry and immunofluorescent staining were used. Western blot, Real-time PCR, RNA interference and overexpression plasmid DNA transfection were performed to investigate the relationship between PTEN and MDH2 as well as the impact of E2 on the expression of PTEN and MDH2, while CCK8, transwell and flow cytometric analysis were carried out to evaluate the proliferation, migration and invasion and apoptosis of endometrial carcinoma cell lines.
  
  
  RESULTS
  Our results demonstrated that as a metabolism related enzyme, MDH2 was overexpressed in endometrial carcinoma tissues and related to the grade of the cancer (P=.038). Western blot, Real-time PCR and immunofluorescent staining revealed MDH2 inhibited the expression of PTEN and was co-localized with PTEN in the cytoplasm of endometrial carcinoma. Proliferation, transwell and apoptosis assay suggested that MDH2 enhanced the proliferation, migration and invasion but inhibited the apoptosis of endometrial cancer cell line through suppressing PTEN. Furthermore, E2 inhibited the expression level of PTEN but enhanced MDH2 via GPR30.
  
  
  CONCLUSIONS
  Our study demonstrated that MDH2, stimulated by estrogen, was involved in the development of PTEN-regulated endometrial carcinoma through GPR30-related pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, No. 100, Haining Road, Shanghai 200080, China; Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China. Electronic address: he_yinyan76@sina.cn.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, No. 100, Haining Road, Shanghai 200080, China; Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China. Electronic address: xi_xiaowei63@sina.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xi