Estrogen-induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER-positive breast cancer cells.
Estrogen-induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER-positive breast cancer cells.
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DOI：
10.1002/ijc.24696
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发表时间：
2010-01-01
影响因子：
6.4
通讯作者：
Dong, Jin-Tang
中科院分区：
文献类型：
--
作者：
Guo, Peng;Dong, Xue-Yuan;Zhao, Ke-Wen;Sun, Xiaodong;Li, Qunna;Dong, Jin-Tang
Kruppel样因子5（KLF 5）通过频繁的基因组缺失和表达失调与人类乳腺癌有关，但KLF 5影响乳腺肿瘤发生的分子机制仍不清楚。本研究旨在检测KLF 5是否以及如何影响乳腺癌细胞中ER的功能。使用不同的细胞系，我们发现恢复表达KLF 5抑制雌激素促进的细胞增殖在ER阳性MCF-7和T-47 D细胞系，但对ER阴性SK-BR-3细胞没有影响。雌激素刺激的ER应答元件介导的报告基因分析和ER靶基因c-MYC和组织蛋白酶D（CSTD）的表达分析表明，KLF 5也抑制了ER的转录活性。染色质免疫沉淀（ChIP）实验表明，KLF 5抑制ERα与c-myc和CSTD启动子的结合。雌激素诱导KLF 5与ERα之间存在相互作用。这些结果表明，KLF 5通过蛋白质相互作用阻断ERα与靶基因启动子的结合，阻止靶基因的诱导，从而抑制ERα在基因调控和细胞增殖中的功能。
Kruppel-like factor 5 (KLF5) is implicated in human breast cancer by frequent genomic deletion and expressional deregulation, but the molecular mechanisms by which KLF5 affects breast tumorigenesis are still unknown. The present study was conducted to examine whether and how KLF5 affects the function of ER in breast cancer cells. Using different cell lines, we found that restored expression of KLF5 inhibited estrogen-promoted cell proliferation in ER-positive MCF-7 and T-47D cell lines but had no effect on ER-negative SK-BR-3 cells. Transcriptional activity of ER was also suppressed by KLF5, as detected by using estrogen-stimulated ER responsive element-mediated reporter assay and expression analysis of ER target genes including c-MYC and cathepsin D (CSTD). Chromatin immunoprecipitation (ChIP) assays showed that KLF5 inhibited ERα binding to the promoter of c-myc and CSTD. Furthermore, estrogen induced an interaction between KLF5 and ERα. These results suggest that KLF5 inhibits the function of ERα in gene regulation and cell proliferation through protein interaction that interrupts the binding of ERα to target gene promoters to prevent target gene induction.
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影响因子：
3.5
作者：
Dong, Xue-Yuan;Rodriguez, Carmen;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang
影响因子：
4.8
作者：
Chen, CS;Sun, XD;Dong, JT
通讯作者：
Dong, JT
影响因子：
4.8
作者：
Guo, Peng;Dong, Xue-Yuan;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang
影响因子：
8
作者：
Nandan, MO;Yoon, HS;Yang, VW
通讯作者：
Yang, VW
影响因子：
4.8
作者：
Guo, Peng;Zhao, Ke-Wen;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang