title: Dual-specificity Phosphatase 1 Deficiency Induces Endometrioid Adenocarcinoma Progression via Activation of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Pathway.
abstract: BACKGROUND
  Previously, we reported that dual-specificity phosphatase 1 (DUSP1) was differentially expressed in endometrioid adenocarcinoma (EEA). However, the role of DUSP1 in EEA progression and the relationship between DUSP1 and medroxyprogesterone (MPA) are still unclear.
  
  
  METHODS
  The expression of DUSP1 in EEA specimens was detected by immunohistochemical analysis. The effect of DUSP1 on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSP1 expression in EEA cells was measured by Western blot.
  
  
  RESULTS
  DUSP1 expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines (Hec1A, Hec1B, RL952, and Ishikawa), the DUSP1 expression was substantially higher in Ishikawa cells than in other cell lines (P < 0.05). Knockdown of DUSP1 promoted Ishikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/Erk) pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells.
  
  
  CONCLUSIONS
  Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP1 may serve as a potential therapeutic target for the treatment of EEA.
authors.affiliation: Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Bao-Rong
authors.initials: BR
authors.lastname: Gao
authors.affiliation: Department of Gynecology, Tongji University School of Medicine Affiliated Shanghai First Maternity and Infant Hospital, Shanghai 200126, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
authors.affiliation: Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jian-Liu
authors.initials: JL
authors.lastname: Wang
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D054637:Dual-Specificity Phosphatases