Regulation of estrogen, interleukin-6 and interleukin-8 in ovarian cancer cells
- VernacularTitle:雌激素与IL-6、IL-8在卵巢癌细胞中的调节作用
- Author:
Yue WANG
;
Jie YANG
;
Yan GAO
;
Lijie DONG
;
Zhi YAO
- Publication Type:Journal Article
- Keywords:
Estrogen;
IL-6;
IL-8;
Ovarian cancer cells
- From:
Chinese Journal of Microbiology and Immunology
2008;28(9):799-804
- CountryChina
- Language:Chinese
-
Abstract:
Objective To discover the reciprocal regulation and its molecular mechanism of estro-gen, IL-6 and IL-8 in ovarian cancer cells. Methods Based on our previous studies, the effect of 17β-estradiol (E2) on the expression levels of IL-6, IL-8 and their respective receptors was investigated. Mean-while, the effect of IL-6/IL-8 on estrogen receptor (ER) expression and estrogen-dependent transcriptional activation was analyzed. Gene expression profile analysis revealed that CAOV-3 and OVCAR-3 cells, which express ER, IL-6 and IL-8 receptors, were suitable models for this study. Results We found that E2 not only enhanced IL-6/IL-8 secretion via NF-κB signaling pathway, but also modulated IL-6 and IL-8 receptors expression. Tamoxifen (Txf), an ER antagonist, completely abolished E2-stimulated IL-6/IL-8 expression. On the other hand, in the absence of estrogen, both cytokines increased ERα expression, decreased ERβ ex-pression, and activated estrogen-dependent transcriptional activation, which was completely blocked by Txf. Pretreatment of OVCAR-3 with p38 MAPK, MEK1/2 or ErbB2 MAPK inhihitors, respectively, IL-6-media-ted ER activation was blocked, while IL-8-indueed ER activation was blocked by Src inhibitor. Conclusion These data suggest that estrogen, IL-6 and IL-8 may form a mutual amplifying signaling which contributes to the growth and development of ovarian carcinoma.
