TY - JOUR
T1 - Hypoxia induces proteasome-dependent degradation of estrogen receptor α in ZR-75 breast cancer cells
AU - Stoner, Matthew
AU - Saville, Bradley
AU - Wormke, Mark
AU - Dean, Dana
AU - Burghardt, Robert
AU - Safe, Stephen
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Regulation of estrogen receptor α (ERα) 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% O2) or hypoxia (1% O2 or cobaltous chloride), and hypoxia significantly increased hypoxia-inducible factor 1α protein within 3 h after treatment, whereas ERα 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 ERα mRNA; however, hypoxic conditions decreased basal and 17βestradiol-induced pS2 gene expression (mRNA levels) and estrogen response element-dependent reporter gene activity in ZR-75 cells. Although 17β-estradiol and hypoxia induce proteasome-dependent degradation of ERα, their effects on transactivation are different, and this may have implications for clinical treatment of mammary tumors.
AB - Regulation of estrogen receptor α (ERα) 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% O2) or hypoxia (1% O2 or cobaltous chloride), and hypoxia significantly increased hypoxia-inducible factor 1α protein within 3 h after treatment, whereas ERα 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 ERα mRNA; however, hypoxic conditions decreased basal and 17βestradiol-induced pS2 gene expression (mRNA levels) and estrogen response element-dependent reporter gene activity in ZR-75 cells. Although 17β-estradiol and hypoxia induce proteasome-dependent degradation of ERα, their effects on transactivation are different, and this may have implications for clinical treatment of mammary tumors.
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U2 - 10.1210/me.2001-0347
DO - 10.1210/me.2001-0347
M3 - Article
C2 - 12351689
AN - SCOPUS:0036795452
VL - 16
SP - 2231
EP - 2242
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 10
ER -