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

Molecular Cancer

Research

Ming Yu¹  Lu Qian¹  Meiru Hu¹  Ming Shi¹  Liang Guo¹  Changguo Chen¹  Beifen Shen¹  Ning Guo¹  Lun Song¹  Huijun Duan²  Dan Liu²  Caili Han²  Bo Wei³ 

[1] Department of Molecular Immunology, Institute of Basic Medical Sciences, 100850, Beijing, P.R. China;Department of Pathology, Hebei Medical University, 050017, Shijiazhuang, P.R. China;Department of Surgery, General Hospital of PLA, Yongding Road 69, Haidian District, 100039, Beijing, P.R. China;

关键词: Gastric Cancer;    Gastric Cancer Cell;    Isoproterenol;    Gastric Cancer Cell Line;    Gastric Cancer Tissue;   

DOI  :  10.1186/1476-4598-9-269

 received in 2010-06-08, accepted in 2010-10-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundStress, 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.ResultsIncreased 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.ConclusionsUp-regulation of MMP-7 expression through β2-AR-mediated signaling pathway is involved in invasion and metastasis of gastric cancer.

【 授权许可】

Unknown   
© Shi et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.