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

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,...

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Autores principales: Shi, Ming, Liu, Dan, Duan, Huijun, Han, Caili, Wei, Bo, Qian, Lu, Chen, Changguo, Guo, Liang, Hu, Meiru, Yu, Ming, Song, Lun, Shen, Beifen, Guo, Ning
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964618/
https://www.ncbi.nlm.nih.gov/pubmed/20939893
http://dx.doi.org/10.1186/1476-4598-9-269
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author Shi, Ming
Liu, Dan
Duan, Huijun
Han, Caili
Wei, Bo
Qian, Lu
Chen, Changguo
Guo, Liang
Hu, Meiru
Yu, Ming
Song, Lun
Shen, Beifen
Guo, Ning
author_facet Shi, Ming
Liu, Dan
Duan, Huijun
Han, Caili
Wei, Bo
Qian, Lu
Chen, Changguo
Guo, Liang
Hu, Meiru
Yu, Ming
Song, Lun
Shen, Beifen
Guo, Ning
author_sort Shi, Ming
collection PubMed
description 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.
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spelling pubmed-29646182010-10-28 Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer Shi, Ming Liu, Dan Duan, Huijun Han, Caili Wei, Bo Qian, Lu Chen, Changguo Guo, Liang Hu, Meiru Yu, Ming Song, Lun Shen, Beifen Guo, Ning Mol Cancer Research 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. BioMed Central 2010-10-12 /pmc/articles/PMC2964618/ /pubmed/20939893 http://dx.doi.org/10.1186/1476-4598-9-269 Text en Copyright ©2010 Shi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research
Shi, Ming
Liu, Dan
Duan, Huijun
Han, Caili
Wei, Bo
Qian, Lu
Chen, Changguo
Guo, Liang
Hu, Meiru
Yu, Ming
Song, Lun
Shen, Beifen
Guo, Ning
Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title_full Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title_fullStr Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title_full_unstemmed Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title_short Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
title_sort catecholamine up-regulates mmp-7 expression by activating ap-1 and stat3 in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964618/
https://www.ncbi.nlm.nih.gov/pubmed/20939893
http://dx.doi.org/10.1186/1476-4598-9-269
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