β-catenin regulates the gene of MMP-26, a novel matrix metalloproteinase expressed both in carcinomas and normal epithelial cells
β-catenin regulates the gene of MMP-26, a novel matrix metalloproteinase expressed both in carcinomas and normal epithelial cells
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DOI：
10.1016/j.biocel.2003.12.007
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Strongin, AY
中科院分区：
文献类型：
--
作者：
Marchenko, ND;Marchenko, GN;Strongin, AY
有几个非正统的特征，区分非冗余和独特的新型基质金属蛋白酶-26（MMP-26）（一种最近进化的酶，不存在于啮齿动物中，但存在于人类中）从MMP超家族的其他成员。本报告描述了我们最近的努力，以获得更好的理解的机制，限制表达MMP-26某些细胞/组织类型。我们研究了人类MMP-26基因在正常和恶性细胞中的转录调控。MMP-26启动子的AP-1和Tcf-4位点似乎在调节HEK 293胚胎肾和MCF 7乳腺癌细胞中MMP-26-荧光素酶嵌合体的表达中最有效。Wnt通路的关键调节因子（β-连环蛋白和与β-连环蛋白相关的淋巴增强子结合因子/T细胞因子）增强了MMP-26的转录活性，表明MMP-26基因可能是Wnt通路的靶点。免疫染色，基因阵列和逆转录聚合酶链反应（RT-PCR）证实MMP-26的存在下，在正常细胞，包括顶端上皮结膜细胞的人的眼睛，以及在恶性上皮细胞的起源。MMP-26主要以其酶原形式积累在转染的乳腺癌MCF 7细胞的细胞内环境中。这项研究使我们朝着更好地了解上皮细胞MMP-26在生理条件和肿瘤中的非常规作用、调节和功能迈出了一步。(C)2004爱思唯尔有限公司保留所有权利。
There are several unorthodox features, which distinguish the non-redundant and unique novel matrix metalloproteinase-26 (MMP-26) (an enzyme that has recently evolved and does not exist in rodents but is present in humans) from other members of the MMP superfamily. This report describes our recent efforts to gain a better understanding of the mechanisms which restrict expression of MMP-26 to certain cell/tissue types. We examined transcriptional regulation of the human MMP-26 gene in normal and malignant cells. The AP-1 and Tcf-4 sites of the MMP-26 promoter appear most potent in regulating the expression of the MMP-26-luciferase chimera in HEK293 embryonic kidney and MCF7 breast carcinoma cells. Key regulators of the Wnt pathway (beta-catenin and lymphoid enhancer-binding factor/T-cell factor with which beta-catenin associates) enhanced the transcriptional activity of MMP-26 suggesting that the MMP-26 gene is a likely target of the Wnt pathway. Immunostaining, gene arrays and reverse-transcriptase polymerase chain reaction (RT-PCR) confirm the presence of MMP-26 in normal cells, including the apical epithelial conjunctiva cells of the human eye, as well as in malignant cells of epithelial origin. MMP-26 predominantly accumulates in its proenzyme form in the intracellular milieu of the transfected breast carcinoma MCF7 cells. This study brings us a step forward towards a better understanding of the unconventional role, regulation and functions of epithelial cell MMP-26 in physiological conditions and in neoplasms. (C) 2004 Elsevier Ltd. All rights reserved.