Overview of matrix metalloproteinase expression in cultured human cells

Overview of matrix metalloproteinase expression in cultured human cells
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DOI:
10.1016/s0945-053x(98)90019-1
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发表时间:
1998-03-01
期刊:
影响因子:
6.9
通讯作者:
Klebe, RJ
Klebe, RJ
中科院分区:
生物学1区
文献类型:
--
作者:
Giambernardi, TA;Grant, GM;Klebe, RJ

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基质金属蛋白酶(matrix metalloproteinases, MMP)通过免疫组化研究和特异性金属蛋白酶抑制剂抑制肿瘤侵袭和转移的观察,已被证实与肿瘤的侵袭和转移有关。优化了13种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)的寡核苷酸引物,用于RT-PCR。采用半定量RT-PCR方法测定了84种正常、转化或致癌物转化的人细胞系和来自不同组织的细胞株中MMP mRNA的表达模式。结果显示一个或多个细胞系表达13个MMP家族成员。此外,还分析了各种致癌基因转染的人成纤维细胞株的MMP表达情况。我们证实了H-ras癌蛋白的过表达与MMP-9的上调相关,并证明了v-sis的过表达也上调了MMP-9。发现myc表达后永生化的细胞系上调了MMP-7、MMP-11和MMP-13。在乳腺、前列腺、骨、结肠和口腔肿瘤来源细胞系中检测到几种MMP mrna的异常表达。鉴定至少一个表达13种MMPs的细胞系,并观察癌基因诱导的几种MMPs的表达,有助于分析控制每种MMP的转录机制。
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.