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Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer

Authors: Ming Shi, Dan Liu, Huijun Duan, Caili Han, Bo Wei, Lu Qian, Changguo Chen, Liang Guo, Meiru Hu, Ming Yu, Lun Song, Beifen Shen, Ning Guo

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Stress, anxiety and depression can cause complex physiological and neuroendocrine changes, resulting in increased level of stress related hormone catecholamine, which may constitute a primary mechanism by which physiological factors impact gene expression in tumors. In the present study, we investigated the effects of catecholamine stimulation on MMP-7 expression in gastric cancer cells and elucidated the molecular mechanisms of the up-regulation of MMP-7 level by catecholamine through an adrenergic signaling pathway.

Results

Increased MMP-7 expression was identified at both mRNA and protein levels in the gastric cancer cells in response to isoproterenol stimulation. β2-AR antigonist effectively abrogated isoproterenol-induced MMP-7 expression. The activation of STAT3 and AP-1 was prominently induced by isoproterenol stimulation and AP-1 displayed a greater efficacy than STAT3 in isoproterenol-induced MMP-7 expression. Mutagenesis of three STAT3 binding sites in MMP-7 promoter failed to repress the transactivation of MMP-7 promoter and silencing STAT3 expression was not effective in preventing isoproterenol-induced MMP-7 expression. However, isoproterenol-induced MMP-7 promoter activities were completely disappeared when the AP-1 site was mutated. STAT3 and c-Jun could physically interact and bind to the AP-1 site, implicating that the interplay of both transcriptional factors on the AP-1 site is responsible for isoproterenol-stimulated MMP-7 expression in gastric cancer cells. The expression of MMP-7 in gastric cancer tissues was found to be at the site where β2-AR was overexpressed and the levels of MMP-7 and β2-AR were the highest in the metastatic locus of gastric cancer.

Conclusions

Up-regulation of MMP-7 expression through β2-AR-mediated signaling pathway is involved in invasion and metastasis of gastric cancer.
Appendix
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Metadata
Title
Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
Authors
Ming Shi
Dan Liu
Huijun Duan
Caili Han
Bo Wei
Lu Qian
Changguo Chen
Liang Guo
Meiru Hu
Ming Yu
Lun Song
Beifen Shen
Ning Guo
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-269

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