pVHL ‐mediated degradation of HIF ‐2α regulates estrogen receptor α expression in normoxic breast cancer cells

Estrogen receptor α ( ER α) 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 ER α protein expression in normoxia and hypoxia. The von Hippel–Lindau protein ( pVHL )‐dependent degradation of HIF ‐2α participates in the regulation of ER α expression. Additionally, HIF ‐2α forms a protein complex with ER α, and amino acids 396–823 of HIF ‐2α physically interact with the ligand‐binding domain of ER α. These results indicate that HIF ‐2α functions as a negative regulator of ER α expression in breast cancer, especially in normoxia.