Metallothionein-2A Overexpression Increases the Expression of Matrix metalloproteinase-9 and Invasion of Breast Cancer Cells

FEBS Lett. 2011 Jan 21;585(2):421-8. doi: 10.1016/j.febslet.2010.12.030. Epub 2010 Dec 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Matrix Metalloproteinase 9 / genetics*
  • Metallothionein / genetics*
  • Metallothionein / physiology
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / genetics*
  • RNA, Small Interfering / pharmacology
  • Transcription Factor AP-1 / metabolism

Substances

  • NF-kappa B
  • RNA, Small Interfering
  • Transcription Factor AP-1
  • Metallothionein
  • Matrix Metalloproteinase 9