pVHL-mediated degradation of HIF-2α regulates estrogen receptor α expression in normoxic breast cancer cells.
Estrogen receptor α (ERα) functions as a transcription factor for genes involved in estrogen-dependent development of breast cancer cells. We demonstrate here that knockdown of hypoxia-inducible factor (HIF)-2α, but not of HIF-1α, increases endogenous ERα protein expression in normoxia and hypoxia. The von Hippel-Lindau protein (pVHL)-dependent degradation of HIF-2α participates in the regulation of ERα expression. Additionally, HIF-2α forms a protein complex with ERα, and amino acids 396-823 of HIF-2α physically interact with the ligand-binding domain of ERα. These results indicate that HIF-2α functions as a negative regulator of ERα expression in breast cancer, especially in normoxia.
Department of Food Science, Ishikawa Prefectural University, Nonoichi, Ishikawa, Japan.|Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasuki
Y
Higashimura
Division of Applied Biological Chemistry, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
Tomoya
T
Kitakaze
Division of Applied Biological Chemistry, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
Naoki
N
Harada
Division of Clinical Nutrition, Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino, Osaka, Japan.
Hiroshi
H
Inui
Center of Research and Development of Bioresources, Osaka Prefecture University, Sakai, Osaka, Japan.
Yoshihisa
Y
Nakano
Division of Applied Biological Chemistry, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
Ryoichi
R
Yamaji
D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D000596:Amino Acids; D051792:Basic Helix-Loop-Helix Proteins; D047628:Estrogen Receptor alpha; D008024:Ligands; D046912:Multiprotein Complexes; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C506487:ESR1 protein, human; C497446:VHL protein, human
estrogen receptor α; hypoxia-inducible factor-2α; von Hippel-Lindau protein