(–)-Epigallocatechin-3-gallate down-regulates EGFR, MMP-2, MMP-9 and EMMPRIN and inhibits the invasion of MCF-7 tamoxifen-resistant cells. Issue 2 (29th October 2010)

• Record Type: Journal Article
• Authors: Farabegoli, Fulvia; Papi, Alessio; Orlandi, Marina
• Is Part Of: Bioscience reports. Volume 31:Issue 2(2011)
• Page Start: 99
• Page End: 108
• Publication Date: 2010-10-29
• Subjects: breast carcinoma -- tamoxifen -- (–)-epigallocatechin-3-gallate (EGCG) -- invasion -- tissue inhibitor of metalloproteinases-1 (TIMP-1) -- receptor tyrosine kinase; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20090143
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : The activation of the EGFR (epidermal growth factor receptor) signalling pathway is one of the key mechanisms underlying the development of resistance to tamoxifen in breast cancer patients. As EGCG [(–)-epigallocatechin-3-gallate], the most active catechin present in green tea, has been shown to down-regulate EGFR, we studied the effects of 10–100 μg/ml EGCG treatment on growth and invasion in a breast carcinoma cell line resistant to tamoxifen [MCF-7Tam (MCF-7 breast carcinoma cell line resistant to tamoxifen) cells] and parental MCF-7. A dose-dependent down-regulation of EGFR mRNA expression and protein level occurred after 50 μg/ml EGCG treatment of MCF-7Tam cells. EGFR molecules on the plasma membrane surface of MCF-7Tam cells significantly decreased. EGFR phosphorylation (Tyr-992, Tyr-1045 and Tyr-1068) was higher in MCF-7Tam than in MCF-7 and it was reduced by EGCG treatment. ERK (extracellular regulated kinase) and phospho-ERK p42/44 were also down-regulated by EGCG treatment and in vitro cell growth and invasion decreased. MMP-2 (matrix metalloproteinase-2) and MMP-9, which are implicated in cell invasion and metastasis, and EMMPRIN (extracellular matrix metalloproteinase inducer), a glycoprotein able to activate MMPs, were significantly reduced after 50 μg/ml EGCG treatment. In keeping with this, TIMP-1 (tissue inhibitor of metalloproteinases-1) and TIMP-2, which down-regulate MMPs, increased after EGCG treatment. Altogether, the present data demonstrated that EGCG could attenuate the tamoxifen-resistant phenotype of MCF-7Tam cells. EGCG could stop MCF-7Tam cell growth and in vitro invasion through down-regulation of EGFR and other molecules implicated in aggressive biological behaviour. The present data support the hypothesis that EGCG is an interesting molecule to be investigated in tamoxifen-resistant breast carcinoma.