IL-6 strengthens Tamoxifen resistance of ovarian cancer cells by promoting ERα-Ser118 phosphorylation though the MEK/ERK pathway
WEI Yiyi
SUN Yang
HUANG Suhui
GUO Xiaoqin
NIU Xiulong
WANG Yue
YANG Jing
FU Zhengying
Abstract：This study was designed to study the effect of IL-6 signal pathway on the phosphorylation of ERα at Ser1 18 site and the transcriptional activity of ERα,and to explore the mechanism of IL-6-induced Tamoxifen (TAM) resistance in ovarian cancer.Human ovarian cancer A2780 cell line with endogenous overexpression of IL-6 and human ovarian cancer CAOV3 cell line with endogenous inhibition of IL-6 expression were obtained by lipofection.The effects of endogenous and exogenous IL-6 on phosphorylation of ERK and Ser118 sites in ERα were detected by Western blot assay;the effect of MEK/ERK signaling pathway of IL-6 on TAM resistance in A2780 cells was detected by MTT assay;the effect of MEK/ ERK signaling pathway of IL-6 on the transcriptional activity of ERα was detected by Luciferase activity assay.Data showed that overexpression of IL-6 upregulated the phosphorylation of ERα-Ser118 in A2780 cells and the inhibition of IL-6 expression downregulated ERα-Ser118 phosphorylation in CAOV3 cells;IL-6 upregulated the phosphorylation of ERK in A2780 cells,and MEK1/2 specific inhibitor PD98059 could reverse the IL-6-mediated ERK and ERα-Ser118 phosphorylation.PD98059 could significantly reduce IL-6-induced resistance to TAM in A2890 cells;IL-6 significantly promoted ERα transcription activity,and PD98059 can reverse this effect.In conclusion,IL-6 phosphorylates Ser118 site of ERα by activating MEK/ERK signaling pathway,promotes ERα transcriptional activity,then activates ER pathway and induces resistance of TAM to OVCA cells.
Keywords：IL-6Ovarian cancerTAM resistanceERαERK
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 294-300 )