Additional MDA-MB-231 breast cancer cell matrix metalloproteinases promote invasiveness
Additional MDA-MB-231 breast cancer cell matrix metalloproteinases promote invasiveness
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DOI：
10.1002/jcp.21417
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发表时间：
2008-08-01
影响因子：
5.6
通讯作者：
Eliceiri, George L.
中科院分区：
文献类型：
--
作者：
Hegedus, Luca;Cho, Hyojin;Eliceiri, George L.
我们感兴趣的是两个方面的特定类型的转移性乳腺癌：哪些潜在的癌症相关基因的表达和哪些因素决定侵袭性。采用逆转录实时荧光定量PCR技术，检测了MDA-MB-231乳腺癌细胞中26种基质金属蛋白酶（MMP）的基因表达，包括MMP-12、MMP-16 variant 2、MMP-19、MMP-20、MMP-21、MMP-23、MMP-24、MMP-25、MMP-25 variant 2、MMP-L1、MMP-26、MMP-27和MMP-28，与迄今为止在这些细胞中检测到的13种MMP形成对比。我们发现，MMP基因在这些细胞中以广泛不同的水平表达，超过五个数量级。在单独的siRNA诱导的消耗后，我们发现另外六种癌细胞MMP促进MDA-MB-231细胞中的侵袭性：MMP-3、MMP-11、MMP-12、MMP-17、MMP-19和MMP-23，从而使在这些细胞中这样做的内源性MMP的总数增加到12种。这些数据支持这样的结论，即一些癌细胞MMP，尽管以低水平表达，但对于MDA-MB-231细胞中的癌症性状是必需的，并且几种内源性MMP在该过程中起非冗余作用。MMP-11的mRNA水平，但不是其他MMP，大幅上升后，个别siRNA靶向的癌细胞MMP-17 mRNA的耗竭，而没有MMP mRNA的增加后，其他MMP mRNA的降解明显。这支持了MMP-17可能是下调MMP-11 mRNA的细胞内信号通路的成员的结论。
We are interested in two aspects of a given type of metastatic breast cancer: which potentially cancer-relevant genes are expressed and which factors determine invasiveness. Using reverse transcription real-time PCR, we detected gene expression of 26 matrix metalloproteinases (MMPs) in MDA-MB-231 breast cancer cells, including those of MMP-12, MMP-16 variant 2, MMP-19, MMP-20, MMP-21, MMP-23, MMP-24, MMP-25, MMP-25 variant 2, MMP-L1, MMP-26, MMP-27, and MMP-28, in contrast to the 13 MMPs detected until now in these cells. We found that MMP genes are expressed at widely different levels in these cells, over five orders of magnitude. After individual siRNA-induced depletions, we found that six additional species of cancer cell MMPs promote invasiveness in MDA-MB-231 cells: MMP-3, MMP-11, MMP-12, MMP-17, MMP-19, and MMP-23, thus raising the total to 12 endogenous MMPs which do so in these cells. The data support the conclusion that some cancer cell MMPs, although expressed at low levels, are needed for cancer trait in MDA-MB-231 cells, and that several endogenous MMPs play non-redundant roles in this process. The mRNA level of MMP-11, but not of other MMPs, rose substantially following individual siRNA-targeted depletion of cancer cell MMP-17 mRNA, while no MMP mRNA increased appreciably after degradation of other MMP mRNAs. This supports the conclusion that MMP-17 may be a member of an intracellular signaling pathway which downregulates MMP-11 mRNA.