Autocrine interferon-γ may affect malignant behavior and sensitivity to tamoxifen of MCF-7 via estrogen receptor β subtype

作者：Niu, Xiu Long; Wang, Yue; Yao, Zhi; Duan, Hongjie; Li, Zhijun; Liu, Wenxing; Zhang, Hongjian; Deng, Wei Min^*

来源：Oncology Reports, 2015, 34(6): 3120-3130.

DOI：10.3892/or.2015.4294

• autocrine
• interferon-gamma
• estrogen receptor beta
• breast cancer cell line MCF-7

Mitogenic actions of estrogens are mediated by two distinct estrogen receptors (ERs), which are critical in the progression and therapeutic response of breast cancer. ER expression is a dynamic phenomenon that is regulated by numerous factors, including cytokines, in the tumor microenvironment. Recently, studies have shown that autocrine production of IL-4 promotes cancer cell growth and there is negative correlation between tumor IL-4 and hormone receptor levels, suggesting that there is crosstalk between cytokine receptors and ER. Thus, we evaluated for interaction between the two ERs and the cytokines IL-4 and IFN-gamma, and if this interaction modulates malignant behavior. We identified that ER beta exerts protective activity in the progression of breast cancer cell line MCF-7, which co-expresses ER alpha and ER beta. IFN-gamma and IL-4 have the opposite effects on malignant biological behavior. Furthermore, we found positive correlation between IFN-gamma and ER beta expression in MCF-7. We also determined that autocrine IFN-gamma in MCF-7 increases mRNA expression of ER beta resulting in enhanced sensitivity to tamoxifen (TAM). These results indicate that ER beta and autocrine IFN-gamma represent two putative targets for breast cancer therapy.

• 出版日期2015-12
• 单位天津医科大学