Giambernardi T A, Grant G M, Taylor G P, Hay R J, Maher V M, McCormick J J, Klebe R J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284, USA.
Matrix Biol. 1998 Mar;16(8):483-96. doi: 10.1016/s0945-053x(98)90019-1.
The matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis both by immunohistochemical studies and from the observation that specific metalloproteinase inhibitors block tumor invasion and metastasis. Oligonucleotide primers for thirteen MMPs (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-15, MMP-16) were optimized for use in RT-PCR. A semi-quantitative RT-PCR assay was used to determine the pattern of MMP mRNA expression in 84 normal and transformed or carcinogen transformed human cell lines and strains derived from different tissues. The results demonstrate one or more cell lines which express thirteen members of the MMP family. In addition, various oncogene transfected human fibroblast cell strains were analyzed for MMP expression. We confirm that over-expression of the H-ras oncoprotein correlates with up-regulation of MMP-9 and demonstrate that over-expression of v-sis also up-regulates MMP-9. A cell line immortalized following myc expression was found to up-regulate MMP-7, MMP-11 and MMP-13. Inappropriate expression of several MMP mRNAs was detected in breast, prostate, bone, colon and oral tumor derived cell lines. Identification of at least one cell line expressing each of thirteen MMPs and the observation of oncogene induced expression of several MMPs should facilitate analysis of the transcriptional mechanisms controlling each MMP.
免疫组化研究以及特定金属蛋白酶抑制剂可阻断肿瘤侵袭和转移这一观察结果均表明,基质金属蛋白酶(MMP)与肿瘤侵袭和转移有关。针对13种MMP(MMP-1、MMP-2、MMP-3、MMP-7、MMP-8、MMP-9、MMP-10、MMP-11、MMP-12、MMP-13、MMP-14、MMP-15、MMP-16)的寡核苷酸引物经优化后用于逆转录聚合酶链反应(RT-PCR)。采用半定量RT-PCR分析方法来确定84种源自不同组织的正常、转化或致癌物转化的人类细胞系和菌株中MMP mRNA的表达模式。结果显示有一个或多个细胞系表达MMP家族的13个成员。此外,还对各种转染了癌基因的人类成纤维细胞系进行了MMP表达分析。我们证实H-ras癌蛋白的过表达与MMP-9的上调相关,并证明v-sis的过表达也会上调MMP-9。发现一个因myc表达而永生化的细胞系上调了MMP-7、MMP-11和MMP-13。在源自乳腺、前列腺、骨、结肠和口腔肿瘤的细胞系中检测到几种MMP mRNA的异常表达。鉴定出至少一个表达13种MMP中每种MMP的细胞系以及观察到癌基因诱导的几种MMP表达,应有助于分析控制每种MMP的转录机制。