J. Cancer Mol. 4: 55-60, 2008

[Research Paper]

Phosphatidylinositol 3-Kinase and NF-kB Involved in Epidermal Growth Factor-Induced Matrix Metalloproteinase-9 Expression

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

Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India

Abstract:

AIM: Matrix metalloproteinase-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 Western blot 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-kB 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 (PI3-K) and nuclear localization of NF-kB 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-kB.  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-kB and PI3-K pathways.  Curcumin was able to down regulate cellular EGFR level and inhibit EGF-induced MMP-9 expression.

(Keywords: EGFR; MMP-9; NF-kB; PI3-K; curcumin)

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Received 9/6/07; Revised 4/7/08; Accepted 5/1/08.

1. Correspondence: Dr. Amitava Chatterjee, Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer Institute, No. 37, S. P. Mukherje Road, Kolkata 700026, India. Fax: 91-33-24757606. E-mail: amitava_chatter@yahoo.co.in

2. Abbreviations: EGF, epidermal growth factor; EGFR, EGF receptor; RTK, receptor tyrosine kinase; ECM, extracellular matrix; MMP, matrix metalloproteinase; PI3-K, phosphatidylinositol 3-kinase.

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