title: Aquaporin-1 plays a crucial role in estrogen-induced tubulogenesis of vascular endothelial cells.
abstract: BACKGROUND
  Aquaporin-1 (AQP1) has been proposed as a mediator of estrogen-induced angiogenesis in human breast cancer and endometrial cancer. Elucidation of the molecular mechanisms governing AQP1-mediated, estrogen-induced angiogenesis may contribute to an improved understanding of tumor development.
  
  
  OBJECTIVE
  Our objective was to identify the estrogen-response element (ERE) in the promoter of the Aqp1 gene and investigate the effects and mechanisms of AQP1 on estrogen-induced tubulogenesis of vascular endothelial cells.
  
  
  METHODS
  The study was conducted in a university hospital in eastern China.
  
  
  METHODS
  Immunohistological, real-time PCR and Western blot analyses were used to determine the expression AQP1 mRNA and protein in vascular endothelial cells. Chromatin immunoprecipitation analyses and luciferase reporter assays identified ERE-like motif in the promoter of the Aqp1 gene.
  
  
  RESULTS
  Expression of AQP1 in blood vessels of human breast and endometrial carcinoma tissues were significantly higher than controls. Estradiol (E2) dose-dependently increased the expression levels of AQP1 mRNA and protein in human umbilical vein endothelial cells (HUVECs). A functional ERE-like motif was identified in the promoter of the Aqp1 gene. AQP1 colocalized with ezrin, a component of the ezrin/radixin/moesin protein complex, and, ezrin colocalized with filamentous actin in HUVECs. Knockdown of AQP1 or ezrin with specific small interfering RNA significantly attenuated the formation of transcytoplasmic filamentous actin stress fibers induced by E2 and inhibited E2-enhanced cell proliferation, migration, invasion, and tubule formation of HUVECs.
  
  
  CONCLUSIONS
  Estrogen induces AQP1 expression by activating ERE in the promoter of the Aqp1 gene, resulting in tubulogenesis of vascular endothelial cells. These results provide new insights into the molecular mechanisms underpinning the angiogenic effects of estrogen.
authors: The Key Laboratory of Reproductive Genetics, Zhejiang University, Hangzhou 310058, China.
authors: Li-Bo
authors: LB
authors: Zou
authors: Shuai
authors: S
authors: Shi
authors: Run-Ju
authors: RJ
authors: Zhang
authors: Ting-Ting
authors: TT
authors: Wang
authors: Ya-Jing
authors: YJ
authors: Tan
authors: Dan
authors: D
authors: Zhang
authors: Xiao-Yang
authors: XY
authors: Fei
authors: Guo-Lian
authors: GL
authors: Ding
authors: Qian
authors: Q
authors: Gao
authors: Cheng
authors: C
authors: Chen
authors: Xiao-Ling
authors: XL
authors: Hu
authors: He-Feng
authors: HF
authors: Huang
authors: Jian-Zhong
authors: JZ
authors: Sheng
mesh_terms: D000328:Adult; D000368:Aged; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D020218:Response Elements / Q000187:drug effects; D055815:Young Adult
chemical_list: D004967:Estrogens; D051398:Aquaporin 1