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Updated: Jul 14, 2026

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
The clock gene Per2 links the circadian system to the estrogen receptor
1Cedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, University of California, Los Angeles, CA 90048, USA. gerys@cshs.org
Abstract:
Circadian rhythms regulate diverse physiological processes including homeostatic functions of steroid hormones and their receptors. Estrogen receptor-alpha (ERalpha) 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 ERalpha signaling network. Binding of enhances ERalpha degradation, while suppression of Per2 levels leads to ERalpha 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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