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Estrogen induces Vav1 expression in human breast cancer cells.

Du MJ, Chen XD, Zhou XL, Wan YJ, Lan B, Zhang CZ, Cao Y - PLoS ONE (2014)

Bottom Line: Nevertheless, two regions at the vav1 gene promoter were defined to be responsible for E2-induced activation of vav1 promoter.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, P. R. China.

ABSTRACT
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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Expression of Vav1 in human breast cancer cell lines.Western Blot analysis of Vav1 and estrogen receptors expression in human breast cancer cell lines (ER positive: MCF7 and T47D; ER negative: MDA-MB-231 and MDA-MB-157) and immortalized breast epithelial line 184A1. The blot with anti-α-tubulin antibody served as a loading control (lower panel). Jurkat cells and its derived vav1- cells (J.Vav1) were used as positive and negative controls for Vav1.
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pone-0099052-g001: Expression of Vav1 in human breast cancer cell lines.Western Blot analysis of Vav1 and estrogen receptors expression in human breast cancer cell lines (ER positive: MCF7 and T47D; ER negative: MDA-MB-231 and MDA-MB-157) and immortalized breast epithelial line 184A1. The blot with anti-α-tubulin antibody served as a loading control (lower panel). Jurkat cells and its derived vav1- cells (J.Vav1) were used as positive and negative controls for Vav1.

Mentions: It was reported previously that Vav1 was detected in ER-positive breast cancer tissue by immunohistochemistry [27]. Here we examined the expression of Vav1 in human breast cancer cell lines (Fig. 1), using Vav1 abundant Jurkat cells as positive control and its derived vav1- cells (J.Vav1) as negative control (Fig. 1, left two lanes). As shown in Figure 1, Vav1 expression appeared high in the two ER positive cell lines, MCF7 and T47D cells, whereas it was barely detectable in MDA-MB-231 and MDA-MB-157, and not detected in the immortalized breast epithelial line 184A1 cells. The estrogen receptors expression of the cell lines was also detected.


Estrogen induces Vav1 expression in human breast cancer cells.

Du MJ, Chen XD, Zhou XL, Wan YJ, Lan B, Zhang CZ, Cao Y - PLoS ONE (2014)

Expression of Vav1 in human breast cancer cell lines.Western Blot analysis of Vav1 and estrogen receptors expression in human breast cancer cell lines (ER positive: MCF7 and T47D; ER negative: MDA-MB-231 and MDA-MB-157) and immortalized breast epithelial line 184A1. The blot with anti-α-tubulin antibody served as a loading control (lower panel). Jurkat cells and its derived vav1- cells (J.Vav1) were used as positive and negative controls for Vav1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048212&req=5

pone-0099052-g001: Expression of Vav1 in human breast cancer cell lines.Western Blot analysis of Vav1 and estrogen receptors expression in human breast cancer cell lines (ER positive: MCF7 and T47D; ER negative: MDA-MB-231 and MDA-MB-157) and immortalized breast epithelial line 184A1. The blot with anti-α-tubulin antibody served as a loading control (lower panel). Jurkat cells and its derived vav1- cells (J.Vav1) were used as positive and negative controls for Vav1.
Mentions: It was reported previously that Vav1 was detected in ER-positive breast cancer tissue by immunohistochemistry [27]. Here we examined the expression of Vav1 in human breast cancer cell lines (Fig. 1), using Vav1 abundant Jurkat cells as positive control and its derived vav1- cells (J.Vav1) as negative control (Fig. 1, left two lanes). As shown in Figure 1, Vav1 expression appeared high in the two ER positive cell lines, MCF7 and T47D cells, whereas it was barely detectable in MDA-MB-231 and MDA-MB-157, and not detected in the immortalized breast epithelial line 184A1 cells. The estrogen receptors expression of the cell lines was also detected.

Bottom Line: Nevertheless, two regions at the vav1 gene promoter were defined to be responsible for E2-induced activation of vav1 promoter.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, P. R. China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus