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

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

doi:10.3892/or.2015.4294

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

Authors:
- Xiu Long Niu
- Yue Wang
- Zhi Yao
- Hongjie Duan
- Zhijun Li
- Wenxing Liu
- Hongjian Zhang
- Wei Min Deng
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Affiliations: Department of Immunology of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Heping, Tianjin, P.R. China, Department of Immunology, Logistics College of Chinese People's Armed Police Forces, Heping, Tianjin, P.R. China
Published online on: September 18, 2015 https://doi.org/10.3892/or.2015.4294
Pages: 3120-3130

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Abstract

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-γ, and if this interaction modulates malignant behavior. We identified that ERβ exerts protective activity in the progression of breast cancer cell line MCF-7, which co-expresses ERα and ERβ. IFN-γ and IL-4 have the opposite effects on malignant biological behavior. Furthermore, we found positive correlation between IFN-γ and ERβ expression in MCF-7. We also determined that autocrine IFN-γ in MCF-7 increases mRNA expression of ERβ resulting in enhanced sensitivity to tamoxifen (TAM). These results indicate that ERβ and autocrine IFN-γ represent two putative targets for breast cancer therapy.

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