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

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.

• Authors: S Gery, R K Virk, K Chumakov, A Yu, H P Koeffler
• Journal: Oncogene (Oncogene) Vol. 26 Issue 57 Pg. 7916-20 (Dec 13 2007) ISSN: 1476-5594 [Electronic] England
• PMID: 17599055 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Nuclear Proteins
• PER2 protein, human
• Period Circadian Proteins
• Transcription Factors

Topics

• Breast Neoplasms (etiology, genetics)
• Cell Line, Tumor
• Circadian Rhythm
• Estrogen Receptor alpha (physiology)
• Female
• Homeostasis
• Humans
• Nuclear Proteins (genetics, physiology)
• Period Circadian Proteins
• Response Elements (physiology)
• Transcription Factors (genetics, physiology)