Estrogen and hypoxia regulate estrogen receptor alpha in a synergistic manner.
Hypoxia activates and degrades estrogen receptor alpha (ERalpha) in human breast cancer cells, which may play an important role in the development and progression of breast cancer. In this study, the synergistic effects of estrogen (E(2)) and hypoxia on ERalpha-mediated transactivation and ERalpha degradation were investigated. ERalpha-mediated transcriptional activity was synergistically increased by E(2) and hypoxia, as determined by the transient expression of ERalpha and ER-responsive reporter plasmids in HEK 293 cells. Twenty hours of E(2) and hypoxia treatment synergistically induced degradation of ERalpha by 95% via a proteasome-dependent pathway in MCF-7 cells. These results provide evidence that hypoxia may stimulate yet unknown factor(s), which can further stimulate ERalpha signal transduction pathways.
Yi
Jinhyung Michael
JM
Department of Bioscience and Biotechnology College of Engineering, Institute of Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, Republic of Korea.
Kwon
Hyeok Yi
HY
Cho
Jung Yoon
JY
Lee
Young Joo
YJ
D000693:Anaerobiosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D015398:Signal Transduction; D014158:Transcription, Genetic
D015853:Cysteine Proteinase Inhibitors; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D007976:Leupeptins; D061988:Proteasome Inhibitors; D004958:Estradiol; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde