期刊
MOLECULAR ENDOCRINOLOGY
卷 16, 期 10, 页码 2231-2242出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2001-0347
关键词
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资金
- NIEHS NIH HHS [ES-04176, ES-09106] Funding Source: Medline
Regulation of estrogen receptor alpha (ERalpha) plays an important role in hormone responsiveness and growth of ER-positive breast cancer cells and tumors. ZR-75 breast cancer cells were grown under conditions of normoxia (21% O-2) or hypoxia (1% O-2 or cobaltous chloride), and hypoxia significantly increased hypoxia-inducible factor 1 a protein within 3 h after treatment, whereas ERalpha protein levels were dramatically decreased within 6-12 h, and this response was blocked by the proteasome inhibitor MG-132. In contrast, hypoxia induced only minimal decreases in cellular Sp1 protein and did not affect ERa mRNA; however, hypoxic conditions decreased basal and 17beta-estradiol- induced pS2 gene expression (mRNA levels) and estrogen response element-dependent reporter gene activity in ZR-75 cells. Although 17beta-estradiol and hypoxia induce proteasome-dependent degradation of ERa, their effects on transactivation are different, and this may have implications for clinical treatment of mammary tumors.
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