Crawford H C, Matrisian L M
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
Enzyme Protein. 1996;49(1-3):20-37. doi: 10.1159/000468614.
Matrix metalloproteinases (MMPs) are expressed in normal remodeling tissues in a generally tissue-restricted pattern. Transcripts for stromelysin-1 and collagenase are expressed primarily in stromal fibroblasts, whereas transcripts for matrilysin are expressed primarily in glandular epithelial cells. These expression patterns are maintained at carcinoma tumor sites until the late stages of tumor progression at which point many epithelially-derived tumors begin to express stromal fibroblast MMPs. Coincidentally, late stage carcinomas take on other characteristics of stromal fibroblasts, indicating that these tumor cells have "transdifferentiated', that is, they have begun to exhibit characteristics of cells from a separate developmental lineage. Despite their distinct expression patterns, many of the promoters for MMP genes show the same general arrangement of the nuclear proto-oncoprotein-binding sites, AP-1 and PEA3. However, the specific interaction between these cis-elements and different combinations of Fos, Jun, and Ets proteins which recognize these sites may be important in controlling both the positive and negative regulation involved in the tissue-restricted pattern of MMP expression in normal and neoplastic tissues.
基质金属蛋白酶（MMPs）在正常组织重塑过程中以通常受组织限制的模式表达。基质溶解素-1和胶原酶的转录本主要在基质成纤维细胞中表达，而基质溶素的转录本主要在腺上皮细胞中表达。这些表达模式在癌瘤部位一直保持到肿瘤进展的晚期，此时许多上皮来源的肿瘤开始表达基质成纤维细胞MMPs。巧合的是，晚期癌瘤呈现出基质成纤维细胞的其他特征，表明这些肿瘤细胞已经“转分化”，也就是说，它们开始表现出来自不同发育谱系细胞的特征。尽管它们的表达模式不同，但许多MMP基因的启动子显示出核原癌蛋白结合位点AP-1和PEA3的相同总体排列。然而，这些顺式元件与识别这些位点的Fos、Jun和Ets蛋白的不同组合之间的特异性相互作用，可能在控制正常和肿瘤组织中MMP表达的组织限制模式所涉及的正负调节方面都很重要。
