Regulation of IL-20 expression by estradiol through KMT2B-mediated epigenetic modification

Chia Hsin Su, I. Hsuan Lin, Tsai Yu Tzeng, Wen Ting Hsieh, Ming Ta Hsu

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumorpromoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer.
原文英語
文章編號e0166090
期刊PLoS One
11
發行號11
DOIs
出版狀態已發佈 - 十一月 1 2016

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)

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