Role of epidermal growth factor receptor/protein kinase B signaling pathway in the generation of tamoxifen resistant MCF-7 breast cancer cells

Abstract

Objective To investigate the change of epidermal growth factor receptor/protein kinase B (EGFR/AKT) signaling pathway in the generation of tamoxifen (TAM) resistant MCF-7 breast cancer cells and the impact on the tumor cell cycle by suppressing EGFR/AKT signaling pathway.Methods The TAM-R was derived from the wild type MCF-7 breast cancer cells continuously exposed to 1 × 10-7 nmol/L 4-hydroxy tamoxifen for 6 months. EGFR mRNA and p-AKT were detected by using fluorescent quantitation reverse transcription-polymerase chain reaction (fqRT-PCR) and Western blotting,respectively.Cell cycle was tested by flow cytometry.Results The expression levels of EGFR mRNA and p-AKT protein in TAM-R cells were higher (P＜0.05) than those in MCF-7 cells.lnhibitors,ZD1839 and SH-6,suppressed the expression of p-AKT and the proliferation of TAM-R cells significantly.Conclusion The activation of EGFR/AKT signaling pathway may provide other growth signal,not estrogen,in tamoxifen resistant MCF-7 cells. Key words: Epidermal growth factor receptor; Protein kinase B; Tamoxifen; Drug resistance; Breast carcinoma