Metallothionein-2A overexpression increases the expression of matrix metalloproteinase-9 and invasion of breast cancer cells.

The overexpression of metallothionein-2A (MT-2A) is frequently observed in invasive human breast tumors and has been linked with more aggressive breast cancers. MT-2A overexpression led to the induction of MDA-MB-231 breast cancer cell migratory and invasive abilities. The reduction of MT-2A expression through small interfering RNA (siRNA) targeting MT-2A in invasive MDA-MB-231 cells completely inhibited both cell invasion and migration. In addition, the expression of matrix metalloproteinase-9 (MMP-9) and the transcriptional activity of AP-1 and NF-κB were upregulated by MT-2A overexpression. Collectively, our results provide the first demonstration that MT-2A promotes breast cancer cell invasion by upregulating MMP-9 via AP-1 and NF-κB activation. Furthermore, we found that MT-2A silencing can inhibit breast cancer invasiveness.