Estrogen regulates anoikis through extracellular signal-regulated kinase (ERK)-focal adhesion kinase (FAK) signaling in MCF-7 breast cancer cells / 基础医学与临床

ABSTRACT

Objective To investigate the effects of estrogen ( E2) on the resistance to anoikis and a possible role of extracellular signal-regulated kinse ( ERK)-focal adhesion kinse ( FAK) signaling in the effect of estrogen to under-stand its underlying mechanism .Methods Poly-Hema-coated culture of human breast cancer cell line MCF-7 was used to induce anoikis .Cells were treated with E2 and/or pretreated with MEK or FAK inhibitors .Western blot was used to assess the phosphorylation of ERK and FAK , trypan blue staining and cell counting were employed to evaluate cell viability , and Hoechst staining was used to check apoptosis .Results Suspension culture greatly re-duced cell survival (P<0.01), and exposure of MCF-7 cells to E2 (10 nmol/L) led to a significantly increased resistance to anoikis and survival ( P<0.05 ) as compared to DMSO .Meanwhile , E2 induced increased phospho-rylation of both ERK and FAK .Pharmacological inhibition of MEK with U 0126 ( 10 μmol/L ) reduced E2-in-creased cell survival by 57.48%(P<0.01) and E2-decreased anoikis;Treatment with FAK inhibitor (10μmol/L) attenuated E2-enhanced cell survival by 53.59% ( P<0.01 ) and E2-reduced apoptosis .Conclusions E2 con-tributes to the enhanced cell viability and increased resistance to anoikis in MCF-7 breast cancer cells , and ERK-FAK signaling may be involved in the E 2-stimulated survival during suspension culture of MCF-7 cells.