title: Identification of estrogen response element in the aquaporin-2 gene that mediates estrogen-induced cell migration and invasion in human endometrial carcinoma.
abstract: BACKGROUND
  Accumulating evidence suggests that aquaporins (AQP) can facilitate cell migration, invasion, and proliferation in tumor development in addition to water transport.
  
  
  OBJECTIVE
  The aim of this study was to examine AQP2 expression in the endometrial tissues from patients with endometrial carcinoma (EC) and determine the roles and mechanisms of AQP2 in estrogen-related cell migration, invasion, adhesion, and proliferation of Ishikawa (IK) cells.
  
  
  METHODS
  AQP2 expression levels were measured in human endometrial cells and estradiol (E(2))-treated IK cells, and the estrogen-response element was identified. After blocking down and up-regulating the endogenous expression of AQP2 in IK cells, cell morphology, capacity for invasion, migration and adhesion, and expression markers of membrane/cytoskeleton were analyzed.
  
  
  RESULTS
  AQP2 was expressed in endometrial tissues from patients with EC and endometriosis, both of which are estrogen-dependent diseases. In IK cells, E(2) dose-dependently increased AQP2 expression, which was blocked by the estrogen receptor inhibitor ICI182780. An estrogen-response element was identified in the AQP2 promoter. E(2) significantly increased the migration, invasion, adhesion, and proliferation of IK cells. AQP2 knockdown attenuated E(2)-enhanced migration, invasion, and adhesion. AQP2 knockdown reduced not only the E(2)-enhanced expression of F-actin and annexin-2 but also the E(2)-induced alteration of cell morphology. Moreover, higher expression levels of F-actin and annexin-2 were detected in the endometrial tissues from patients with EC.
  
  
  CONCLUSIONS
  AQP2 mediates E(2)-enhanced migration, invasion, and adhesion through alteration of F-actin and annexin-2 expression and reorganization of F-actin, and inhibition of AQP may be a potential method for antitumor therapy.
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang 310006, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Zou
authors.forename: Run-Ju
authors.initials: RJ
authors.lastname: Zhang
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Tan
authors.forename: Guo-Lian
authors.initials: GL
authors.lastname: Ding
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Rong-Huan
authors.initials: RH
authors.lastname: He
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Liu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wang
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D051399:Aquaporin 2 / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D020218:Response Elements / Q000187:drug effects / Q000235:genetics*
chemical_list: C472822:ANXA2 protein, human; D000199:Actins; D017306:Annexin A2; D051399:Aquaporin 2; D004967:Estrogens; D004958:Estradiol