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 understand 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 where needed. Western blotting 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 verify apoptosis. Results Suspension culture greatly reduced cell survival (P<0.01), and exposure of MCF-7 cells to E2 (10 nM) led to a significantly increased resistance to anoikis and survival (P<0.05) compared to DMSO. Meanwhile, E2 induced increased phosphorylation of both ERK and FAK. Pharmacological inhibition of MEK with U0126 (10 μM) reduced E2-increased cell survival by 57.48% (P<0.01) and E2-decreased anoikis; Treatment with FAK inhibitor (10 μM) attenuated E2-enhanced cell survival by 53.59% (P<0.01) and E2-reduced apoptosis. Conclusion E2 contributes to enhanced cell viability and increased resistance to anoikis in MCF-7 breast cancer cells, and ERK-FAK signaling may be involved in the E2-stimulated survival during suspension culture of MCF-7 cells.

Key words: estrogen, extracellular signal-regulated kinse, focal adhesion kinse, anoikis, breast cancer cells