Phosphatidylinositol 3-kinase and NF-κB involved in epidermal growth factor-induced Matrix metalloproteinase-9 expression

Shuvojit Moulik, Triparna Sen, Anindita Dutta, Aniruddha Banerji, Chinmoy Ghosh, Shamik Das, Amitava Chatterjee

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Aim: Matrix metalloprotelnase-9 (MMP-9) is a zinc-dependent endopeptidase that is capable of digesting the components of extracellular matrix and basement membrane influencing cancer cell invasion and metastasis. This study is to investigate the signaling pathways responsible for epidermal growth factor (EGF)-induced MMP-9 expression. Methods: Gelatinase zymography, RT-PCR, and Wetern biot analysis were exploited to detect the induction of MMP-9 expression in EGF-treated human breast cancer MDA-MB-231 cells. EGF-induced nuclear translocation of EGF receptor (EGFR) and NF-κB was demonstrated by immunofluorescence. Results: EGF induced nuclear translocation of EGFR and gene expression of MMP-9 in MDA-MB-231 cells. Phosphorylation of phosphatidylinositol 3-kinase (P13-K) and nuclear localization of NF-κB were also observed with EGF-treated MDA-MB-231 cells EGF-induced MMP-9 expression was significantly prevented by the inhibitors against PI3-K or NF-κB. When MDA-MB-231 cells were treated with curcumin prior to the EGF treatment, cellular EGFR level was drastically reduced and EGF-induced MMP-9 expression was also efficiently prevented. Conclusion: EGF induced expression of MMP-9 in MDA-MB-231 cells through the NF-κB and PI3-K pathways. Curcumin was able to down regulate cellular EGFR level and inhibit EGF-induced MMP-9 expression.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalJournal of Cancer Molecules
Volume4
Issue number2
StatePublished - 2008
Externally publishedYes

Keywords

  • Curcumin
  • EGFR
  • MMP-9
  • NF-κB
  • P13-K

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