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基质金属蛋白酶9基因多态性与胃癌风险概述

An Overview of Matrix Metalloproteinase 9 Polymorphism and Gastric Cancer Risk.

作者信息

Verma Sugreev, Kesh Kousik, Gupta Arnab, Swarnakar Snehasikta

机构信息

Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(17):7393-400. doi: 10.7314/apjcp.2015.16.17.7393.

Abstract

Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position -1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9 -1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.

摘要

基质金属蛋白酶(MMP)9是锌依赖性内肽酶多功能家族的关键成员,已发现在炎症期间和某些癌症中其表达上调。MMP可切割细胞外基质(ECM)蛋白,并在细胞凋亡、血管生成、肿瘤生长和转移中发挥关键作用。已鉴定出几种基因多态性,这些多态性对MMP9调节具有等位基因特异性影响,并与胃癌相关,胃癌是世界上第四大常见恶性肿瘤。除幽门螺杆菌感染外,遗传易感性是另一个已记录的胃癌危险因素。MMP9基因-1562C/T位点的单核苷酸多态性(SNP)导致转录因子与MMP9基因启动子结合的调节,从而引起蛋白质表达和酶活性的差异。尽管多项研究已证明MMP9 -1562 C/T多态性与不同疾病之间存在关联,但胃癌发生过程中MMP9的转录调控仍知之甚少。了解胃癌期间MMP9上调的机制可能为诊断和治疗提供新的范例。

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