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pVHL ‐mediated degradation of HIF ‐2α regulates estrogen receptor α expression in normoxic breast cancer cells
Author(s) -
Higashimura Yasuki,
Kitakaze Tomoya,
Harada Naoki,
Inui Hiroshi,
Nakano Yoshihisa,
Yamaji Ryoichi
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12265
Subject(s) - estrogen receptor , gene knockdown , transcription factor , chemistry , microbiology and biotechnology , hypoxia inducible factors , estrogen receptor alpha , receptor , regulator , cancer research , estrogen , biology , breast cancer , gene , endocrinology , cancer , biochemistry , genetics
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.