DESCRIPTION

The activation of Epidermal Growth Factor Receptor (EGFR) signaling pathway is one of the key mechanisms underlying the development of resistance to tamoxifen in breast cancer patients. As -(-) Epigallocatechine-3-gallate (EGCG), the most active catechin present in green tea, has been shown to downregulate 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) and parental MCF-7. A dose-dependent downregulation 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 phoshoporylation (Tyr992, Tyr1045 and Tyr1068) was higher in MCF-7Tam than MCF-7 and it was reduced by EGCG treatment. ERK and phosphoERK p42/44 were also dowregulated by EGCG treatment and in vitro cell growth and invasion decreased. Matrix Metalloproteinases (MMPs) -2 and -9, which are implicated in cell invasion and metastasis and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN), a glycoprotein able to activate MMPs, were significantly reduced after 50 µg/ml EGCG treatment. Coherently, Tissue Inhibitors of Metallo Proteinases (TIMPs) -1 and -2, which downregulate MMPs, increased after EGCG treatment.

Altogether the present data demonstrated that EGCG could attenuate the tamoxifen-resistant phenotype of MCF-7Tam cells. EGCG could contrast MCF-7Tam cell growth and in vitro invasion through downregulation of EGFR and other molecules implicated in aggressive biologic behavior. The present data support the hypothesis that EGCG is an interesting molecule to be investigated in tamoxifen-resistant breast carcinoma.

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