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Heregulin-β promotes matrix metalloproteinase-7 expression via HER2-mediated AP-1 activation in MCF-7 cells

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Abstract

It has been reported that HER2 level is strongly correlated with the expression of MMP-7 in some carcinomas. HER2 is a preferred heterodimerization partner of EGFR, HER3, and HER4. HER2 overexpression is believed to enhance the signaling from these receptors in response to binding of their specific ligands. In this study, we show that heregulin-β (HRG-β) stimulation remarkably induced MMP-7 promoter activity and significantly enhanced the expression and activity of MMP-7 in MCF-7 cells overexpressing HER2. The expression of c-Jun and c-Fos and the level of the phosphorylated c-Jun were markedly increased after HRG-β treatment in MCF-7/HER2 cells. Increased MMP-7 promoter activity was observed in MCF-7/c-Jun cells. The activity of the MMP-7 promoter induced by HRG-β in MCF-7/HER2 cells could be inhibited by a dominant negative c-Jun mutant TAM67 and by the mutagenesis of the AP-1 site. c-Jun binding to MMP-7 promoter was confirmed by ChIP assays. The data indicate a close link among HRG-β stimulation, HER signaling, and AP-1 activation. Our data suggest that HRG-β-induced MMP-7 expression was regulated by HER2-mediated AP-1 activation in MCF-7 cells.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 30771981), Beijing Natural Science Foundation (No. 708270), and National Basic Research Program of China (973 Program, No. 2006CB504305).

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, Taiping Road 27, Beijing, 100850, People’s Republic of China

    Guogang Yuan, Lu Qian, Lun Song, Ming Shi, Dan Li, Ming Yu, Meiru Hu, Beifen Shen & Ning Guo

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  1. Guogang Yuan
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Correspondence to Ning Guo.

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Yuan, G., Qian, L., Song, L. et al. Heregulin-β promotes matrix metalloproteinase-7 expression via HER2-mediated AP-1 activation in MCF-7 cells. Mol Cell Biochem 318, 73–79 (2008). https://doi.org/10.1007/s11010-008-9858-6

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