Lochter A, Sternlicht M D, Werb Z, Bissell M J
Life Sciences Division, Lawrence Berkeley National Laboratory, University of California 94720, USA.
Ann N Y Acad Sci. 1998 Oct 23;857:180-93. doi: 10.1111/j.1749-6632.1998.tb10116.x.
Matrix metalloproteinases (MMPs) orchestrate tissue remodeling and play diverse roles during organ development. They are produced excessively during the course of various pathological conditions, including solid tumors. An important function of MMPs during tumor progression is to provide the proteolytic activity that is necessary both for tumor cells to invade extracellular matrix (ECM) and for neovascularization of tumor tissue by endothelial cells. Recently, independent studies in transgenic animals suggest that MMPs may, in addition, promote very early stages of tumor progression. To investigate this possibility further, we have analyzed the consequences of MMP overexpression in functionally normal and nontumorigenic mouse mammary epithelial cells in culture. Our observations demonstrate that the MMP stromelysin-1 (SL-1) triggers an epigenetic molecular program in mammary epithelial cells that results in a number of phenotypic alterations that eventually culminate in the generation of a malignant tumor-cell phenotype.
基质金属蛋白酶（MMPs）协调组织重塑，并在器官发育过程中发挥多种作用。在包括实体瘤在内的各种病理状况下，它们会过度产生。MMPs在肿瘤进展过程中的一个重要功能是提供蛋白水解活性，这对于肿瘤细胞侵入细胞外基质（ECM）以及内皮细胞对肿瘤组织进行新血管生成都是必需的。最近，在转基因动物中的独立研究表明，MMPs此外还可能促进肿瘤进展的非常早期阶段。为了进一步研究这种可能性，我们分析了在功能正常且无致瘤性的培养小鼠乳腺上皮细胞中MMP过表达的后果。我们的观察结果表明，MMP基质溶解素-1（SL-1）在乳腺上皮细胞中触发了一个表观遗传分子程序，导致许多表型改变，最终 culminate在产生恶性肿瘤细胞表型上。 （注：“culminate”此处可能有误，结合语境推测可能是“最终导致”之类意思，可根据准确原文修正译文）
