Differences between integrin alpha 5 beta 1 and EGRF receptor in signal pathways controlling proliferation and apoptosis of MCF-7/Dox human breast carcinoma cells

In MCF-7/Dox human breast carcinoma cells, down-regulation of integrin alpha 5 beta 1 and inhibition of epidermal growth factor receptor (EGFR) markedly reduced cell proliferation. Cell cycle analysis showed that alpha 5 beta 1 down-regulation resulted in cycle arrest at the S-phase, followed by a significant increase in the population of apoptotic cells (subG sub(1) population). Inhibition of EGFR activity also caused cell cycle arrest at the S-phase but without any increase in the subG sub(1) population. Down-regulation of alpha 5 beta 1 and EGFR inhibition resulted in a significant decrease of cell content of the active (phosphorylated) forms of FAK and Erk protein kinases. The data obtained suggest that alpha 5 beta 1 integrin is implicated in cell growth control via inhibition of apoptotic cell death and through EGFR activation.