Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.

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 α (...

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Main Authors: Liyun Xiao, Alan K Chang, Ming-Xi Zang, Hailian Bi, Shujing Li, Miao Wang, Xinrong Xing, Huijian Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095878&type=printable
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author Liyun Xiao
Alan K Chang
Ming-Xi Zang
Hailian Bi
Shujing Li
Miao Wang
Xinrong Xing
Huijian Wu
author_facet Liyun Xiao
Alan K Chang
Ming-Xi Zang
Hailian Bi
Shujing Li
Miao Wang
Xinrong Xing
Huijian Wu
author_sort Liyun Xiao
collection DOAJ
description 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 α (E2-ERα) signaling in ERα-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ERα and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples. Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα. In these cells, E2 promoted the binding of ERα to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERα-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells.
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spelling doaj-art-51a7d16b7da64b088538cffa8f1776d52025-08-20T03:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9587810.1371/journal.pone.0095878Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.Liyun XiaoAlan K ChangMing-Xi ZangHailian BiShujing LiMiao WangXinrong XingHuijian WuGrowing 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 α (E2-ERα) signaling in ERα-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ERα and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples. Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα. In these cells, E2 promoted the binding of ERα to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERα-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095878&type=printable
spellingShingle Liyun Xiao
Alan K Chang
Ming-Xi Zang
Hailian Bi
Shujing Li
Miao Wang
Xinrong Xing
Huijian Wu
Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
PLoS ONE
title Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
title_full Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
title_fullStr Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
title_full_unstemmed Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
title_short Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.
title_sort induction of the clock gene by e2 erα signaling promotes the proliferation of breast cancer cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095878&type=printable
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