A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in endometrial carcinomas
A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in endometrial carcinomas
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DOI：
10.1111/j.1349-7006.2000.tb00989.x
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发表时间：
2000-06-01
期刊：
影响因子：
--
通讯作者：
Kudo, R
中科院分区：
文献类型：
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作者：
Nishioka, Y;Kobayashi, K;Kudo, R
最近的研究表明，基质金属蛋白酶-1启动子的单鸟嘌呤插入多态性产生了一个Ets结合位点，并影响基质金属蛋白酶-1 （matrix metalloproteinase-1, MMP-1）转录水平的升高。此外，在来自黑色素瘤和乳腺癌的肿瘤细胞系中，2G/2G基因型的发生率明显高于正常人群。为了评估这种多态性在子宫内膜癌中的作用，我们对100例子宫内膜癌进行了基因分型，然后分析了MMP-1在这些癌中的免疫表达。我们发现子宫内膜癌患者1G/2G或2G/2G基因型的发生率明显高于对照个体，并且含有2G等位基因(a)的肿瘤比含有1G/1G基因型的肿瘤更频繁地表达MMP-1蛋白。因此，MMP-1启动子的单核苷酸多态性影响了MMP-1蛋白的表达水平，这可能导致子宫内膜癌更具侵袭性。我们的研究结果表明，MMP-1启动子2G多态性的存在可能是子宫内膜癌发生和/或进展的危险因素之一。
Recent studies demonstrated that a single guanine insertion polymorphism in a matrix metallopretease-1 promoter created an Ets binding site and affected the elevation of the transcriptional level of matrix metalloproteinase-1 (MMP-1). Furthermore, in tumor cell lines derived from melanoma and breast cancer, the incidence of the 2G/2G genotype was significantly higher than that in the normal population, To evaluate the contribution of this polymorphism in endometrial carcinomas, we genotyped 100 endometrial carcinomas and then analyzed immunoexpression of MMP-1 in these carcinomas. We found that endometrial carcinoma patients showed a significantly higher rate of 1G/2G or 2G/2G genotype than control individuals, and that tumors containing the 2G allele(a) expressed MMP-1 protein more frequently than those,vith 1G/1G genotype. Therefore, the single nucleotide polymorphism at the MMP-1 promoter affected the expression level of the MMP-1 protein, which may result in the association with more aggressive character in endometrial carcinoma. Our result suggests that the presence of 2G polymorphism at the, MMP-1 promoter may be one of the risk factors for the development and/or progression of endometrial carcinoma.