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论文类型：期刊论文

发表时间：2014-05-02

发表刊物：PLOS ONE

收录刊物：SCIE、PubMed、Scopus

卷号：9

期号：5

页面范围：e95878

ISSN号：1932-6203

摘要：Growing genetic and epidemiological evidence suggests a direct connection between the disruption of circadian rhythm and breast cancer. Moreover, the expression of several molecular components constituting the circadian clock machinery has been found to be modulated by estrogen-estrogen receptor alpha (E2-ER alpha) signaling in ER alpha-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ER alpha and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ER alpha-positive breast tumor samples. Subsequent experiments using ER alpha-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ER alpha. In these cells, E2 promoted the binding of ER alpha to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERa-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells.