The clock gene Per2 links the circadian system to the estrogen receptor

被引：0
作者：
S Gery
R K Virk
K Chumakov
A Yu
H P Koeffler
机构：
[1] Cedars-Sinai Medical Center,Division of Hematology/Oncology
[2] UCLA School of Medicine,undefined
[3] University of California,undefined
来源：
Oncogene | 2007年 / 26卷
关键词：
circadian rhythms; ER; breast cancer; Per2; transcriptional activation; estrogen;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Circadian rhythms regulate diverse physiological processes including homeostatic functions of steroid hormones and their receptors. Estrogen receptor-α (ERα) is essential for normal mammary gland physiology and is a prognostic marker for the treatment of breast cancer. We report that Per2, a core clock gene, links the circadian cycle to the ERα signaling network. Binding of enhances ERα degradation, while suppression of Per2 levels leads to ERα stabilization. In turn, Per2 itself is estrogen inducible in these cells, suggesting a feedback mechanism to attenuate stimulation by estrogen. In addition, overexpression of Per2 in breast cancer cells leads to significant growth inhibition, loss of clonogenic ability and apoptosis. Taken together, these results further support a critical role for peripheral circadian regulation in tissue homeostasis and suggest a novel role for clock genes in estrogen receptor-positive breast cancer.
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页码：7916 / 7920
页数：4
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