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Metallothionein‐2A overexpression increases the expression of matrix metalloproteinase‐9 and invasion of breast cancer cells
Author(s) -
Kim Hyung Gyun,
Kim Jin Young,
Han Eun Hee,
Hwang Yong Pil,
Choi Jae Ho,
Park Bong Hwan,
Jeong Hye Gwang
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.12.030
Subject(s) - gene silencing , small interfering rna , metallothionein , cancer research , downregulation and upregulation , matrix metalloproteinase , breast cancer , matrix metalloproteinase 9 , cell , cancer , chemistry , biology , medicine , cell culture , transfection , gene , biochemistry , genetics
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.