Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk
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| Creator |
Kesh, Kousik
Subramanian, Lakshmi Ghosh, Nillu Gupta, Vinayak Gupta Gupta, Arnab Bhattacharya, Samir Mahapatra, Nitish R. Swarnakar, Snehasikta |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
Elevated expression of matrix metalloproteinase7 (MMP7)
has been demonstrated to play a pivotal role in cancer invasion.The�181A3G(rs11568818) polymorphism in theMMP7promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of�181A3G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n �520). The GG genotype as compared with the AA genotype was predisposed (p � 0.02; odds ratio � 1.9, 95% confidence interval1.1–3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p � 0.03, odds ratio � 2.46, and 95% confidence interval � 1.07–5.68). Metaanalysis
revealed that tobacco enhanced the risk for cancer more
markedly in AG and GG carriers. Activity and expression of
MMP7 were significantly higher in GG than in AA carriers. In
support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine- induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the �181G than the �181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer.
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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2222/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY__Volume_290___Issue_23___Pages_14391%2D14406_;2015[5].pdf
Kesh, Kousik and Subramanian, Lakshmi and Ghosh, Nillu and Gupta, Vinayak Gupta and Gupta, Arnab and Bhattacharya, Samir and Mahapatra, Nitish R. and Swarnakar, Snehasikta (2015) Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk. The Journal of Biological Chemistry, 290 (23). pp. 14391-14406. |
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| Relation |
http://dx.doi.org/10.1074/jbc.M114.630129
http://www.eprints.iicb.res.in/2222/ |
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