In MCF-7/Dox human breast carcinoma cells, down-regulation of integrin alpha5beta1 and inhibition of epidermal growth factor receptor (EGFR) markedly reduced rates of cell proliferation. Mitotic cycle analysis showed that alpha5beta1 down-regulation resulted in cell cycle arrest at the S phase, followed by a significant increase in the population of apoptotic cells (subG1 population). Inhibition of EGFR activity also caused cell cycle arrest at the S-phase but without any increase in the subG1 population. Down-regulation of alpha5beta1 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 alpha5beta1 integrin is implicated in cell growth control via inhibition of apoptotic cell death and through EGFR activation.
Blokirovanie ékspressii integrina al'fa5beta1 i tormozhenie aktivnosti retseptora épidermal'nogo faktora rosta (EGFR) v linii MCF-7/Dox kartsinomy molochnoĭ zhelezy cheloveka soprovozhdaiutsia znachitel'nym snizheniem skorosti proliferatsii kletok. Analiz mitoticheskogo tsikla pokazal, chto snizhenie ékspressii al'fa5beta1 privodilo k zaderzhke tsikla v S faze i soprovozhdalos' sushchestvennym uvelicheniem populiatsii apoptoticheskikh kletok (fraktsii sub-G1). Ingibirovanie aktivnosti EGFR takzhe privodilo k zaderzhke v S faze, no bez uvelicheniia fraktsii sub-G1. Blokirovanie al'fa5beta1 i ingibirovanie EGFR privodilo k umen'sheniiu soderzhaniia aktivnykh (fosforilirovannykh) form kinazy fokal'nogo kontakta FAK i Erk. Rezul'taty pokazyvaiut, chto integrin al'fa5beta1 kontroliruet rost issleduemykh kletok putem tormozheniia ikh apoptoticheskoĭ gibeli i putem aktivatsii EGFR.
Keywords: cell proliferation; growth factors; integrins; oncogenesis; signaling.