Estrogen induces Vav1 expression in human breast cancer cells.
Estrogen induces Vav1 expression in human breast cancer cells.
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雌激素诱导人乳腺癌细胞中 Vav1 的表达
DOI：
10.1371/journal.pone.0099052
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Du MJ;Chen XD;Zhou XL;Wan YJ;Lan B;Zhang CZ;Cao Y
Vav 1是Rho家族GTP酶的鸟嘌呤核苷酸交换因子（GEF），是一种参与多种细胞事件的造血蛋白。近年来，在包括人乳腺癌在内的非造血系统癌症中，已经报道了Vav 1的异常表达。Vav 1如何表达以及Vav 1在其非驻留组织中的作用仍有待回答。本研究旨在探讨Vav 1在乳腺癌细胞中的表达与雌激素-雌激素受体通路的关系。我们不仅验证了Vav 1在人乳腺癌细胞系中的异位表达，而且观察到Vav 1在ER阳性细胞系中的表达受典型的雌激素受体（ER）配体17β-雌二醇（E2）诱导。另一方面，选择性雌激素受体调节剂（SERM）他莫昔芬和ER拮抗剂ICI 182，780抑制Vav 1的表达。雌激素受体调节Vav 1的表达被鉴定为α型，而不是β型。此外，E2处理通过增强启动子活性来增加vav 1基因的转录，尽管没有可识别的雌激素反应元件（ERE）。然而，在vav 1基因启动子的两个区域被定义为负责E2诱导的vav 1启动子的激活。染色质免疫沉淀（ChIP）和免疫共沉淀（Co-IP）分析表明ERα可能通过与转录因子c-Myb和ELF-1相互作用进入vav 1启动子。Vav 1的表达增强导致Cyclin D1的表达升高，细胞周期进程加快。本研究提示雌激素-ER调节Vav 1的转录和表达，这可能有助于癌细胞的增殖。
Vav1, a guanine nucleotide exchange factor (GEF) for Rho family GTPases, is a hematopoietic protein involved in a variety of cellular events. In recent years, aberrant expression of Vav1 has been reported in non-hematopoietic cancers including human breast cancer. It remains to be answered how Vav1 is expressed and what Vav1 does in its non-resident tissues. In this study, we aimed to explore the mechanism for Vav1 expression in breast cancer cells in correlation with estrogen-ER pathway. We not only verified the ectopic expression of Vav1 in human breast cancer cell lines, but also observed that Vav1 expression was induced by 17β-estradiol (E2), a typical estrogen receptor (ER) ligand, in ER-positive cell lines. On the other hand, Tamoxifen, a selective estrogen receptor modulator (SERM), and ICI 182,780, an ER antagonist, suppressed the expression of Vav1. The estrogen receptor modulating Vav1 expression was identified to be α form, not β. Furthermore, treatment of E2 increased the transcription of vav1 gene by enhancing the promoter activity, though there was no recognizable estrogen response element (ERE). Nevertheless, two regions at the vav1 gene promoter were defined to be responsible for E2-induced activation of vav1 promoter. Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) analyses suggested that ERα might access to the vav1 promoter via interacting with transcription factors, c-Myb and ELF-1. Consequently, the enhanced expression of Vav1 led to the elevation of Cyclin D1 and the progression of cell cycle. The present study implies that estrogen-ER modulates the transcription and expression of Vav1, which may contribute to the proliferation of cancerous cells.
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影响因子：
3.7
作者：
Ilan L;Katzav S
通讯作者：
Katzav S
DOI：
10.1186/1477-7800-5-23
发表时间：
2008-10-16
期刊：
International seminars in surgical oncology : ISSO
影响因子：
--
作者：
Lane, Jane;Martin, Tracey A;Jiang, Wen G
通讯作者：
Jiang, Wen G
影响因子：
3.7
作者：
Chan HS;Chang SJ;Wang TY;Ko HJ;Lin YC;Lin KT;Chang KM;Chuang YJ
通讯作者：
Chuang YJ
影响因子：
11.4
作者：
KATZAV, S;MARTINZANCA, D;BARBACID, M
通讯作者：
BARBACID, M
影响因子：
50.3
作者：
Fernandez-Zapico, ME;Gonzalez-Paz, NC;Billadeau, DD
通讯作者：
Billadeau, DD