title: Estrogen receptor beta inhibits transcriptional activity of hypoxia inducible factor-1 through the downregulation of arylhydrocarbon receptor nuclear translocator.
abstract: BACKGROUND
  Estrogen receptor (ER) β is predicted to play an important role in prevention of breast cancer development and metastasis. We have shown previously that ERβ inhibits hypoxia inducible factor (HIF)-1α mediated transcription, but the mechanism by which ERβ works to exert this effect is not understood.
  
  
  METHODS
  Vascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assays. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting, immunoprecipitation, luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to ascertain the implication of ERβ on HIF-1 function.
  
  
  RESULTS
  In this study, we found that the inhibition of HIF-1 activity by ERβ expression was correlated with ERβ's ability to degrade aryl hydrocarbon receptor nuclear translocator (ARNT) via ubiquitination processes leading to the reduction of active HIF-1α/ARNT complexes. HIF-1 repression by ERβ was rescued by overexpression of ARNT as examined by hypoxia-responsive element (HRE)-driven luciferase assays. We show further that ERβ attenuated the hypoxic induction of VEGF mRNA by directly decreasing HIF-1α binding to the VEGF gene promoter.
  
  
  CONCLUSIONS
  These results show that ERβ suppresses HIF-1α-mediated transcription via ARNT down-regulation, which may account for the tumour suppressive function of ERβ.
authors: Department of Bioscience and Biotechnology, College of Life Science, Institute of Biotechnology, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Korea.
authors: Wonchung
authors: W
authors: Lim
authors: Yeomyung
authors: Y
authors: Park
authors: Jungyoon
authors: J
authors: Cho
authors: Choa
authors: C
authors: Park
authors: Joonwoo
authors: J
authors: Park
authors: Young-Kwon
authors: YK
authors: Park
authors: Hyunsung
authors: H
authors: Park
authors: Youngjoo
authors: Y
authors: Lee
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054875:Ubiquitination; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D047629:Estrogen Receptor beta; D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator