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基质金属蛋白酶启动子中2G单核苷酸多态性增强正常基质细胞基因表达的可能性。

Potential for the 2G single nucleotide polymorphism in the promoter of matrix metalloproteinase to enhance gene expression in normal stromal cells.

作者信息

Wyatt Colby A, Coon Charles I, Gibson Jennifer J, Brinckerhoff Constance E

机构信息

Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755-3833, USA.

出版信息

Cancer Res. 2002 Dec 15;62(24):7200-2.

PMID:12499258
Abstract

The 1G/2G polymorphism of matrix metalloproteinase 1 (MMP-1) affects activity of the promoter in transient transfections, and has been associated with the incidence or invasiveness of five types of cancer. In light of these findings, and because stromal cells may contribute to tumor cell invasion, we used quantitative real-time reverse transcription-PCR to measure endogenous MMP-1 mRNA expression in 34 human foreskin fibroblasts homozygous or heterozygous for the 1G and 2G alleles. We measured basal, cytokine, and growth factor induced MMP-1 mRNA expression. The genotype of the MMP-1 promoter polymorphism was not predictive of mean MMP-1 mRNA expression. However, within the population of cell lines with at least one 2G polymorphism, there were more individuals with higher levels of MMP-1 mRNA after treatment with a cytokine or growth factors. Our data suggest that the presence of the 2G polymorphism does not significantly affect mean expression levels of a population but may increase the potential for an individual to have higher MMP-1 expression in response to growth factors and cytokines.

摘要

基质金属蛋白酶1(MMP-1)的1G/2G多态性在瞬时转染中影响启动子活性,并与五种类型癌症的发病率或侵袭性相关。鉴于这些发现,并且由于基质细胞可能有助于肿瘤细胞侵袭,我们使用定量实时逆转录PCR来测量34个人包皮成纤维细胞中1G和2G等位基因纯合或杂合的内源性MMP-1 mRNA表达。我们测量了基础、细胞因子和生长因子诱导的MMP-1 mRNA表达。MMP-1启动子多态性的基因型不能预测平均MMP-1 mRNA表达。然而,在至少有一个2G多态性的细胞系群体中,在用细胞因子或生长因子处理后,有更多个体的MMP-1 mRNA水平较高。我们的数据表明,2G多态性的存在不会显著影响群体的平均表达水平,但可能增加个体对生长因子和细胞因子产生更高MMP-1表达的可能性。

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