title: Autocrine interferon-γ may affect malignant behavior and sensitivity to tamoxifen of MCF-7 via estrogen receptor β subtype.
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.
authors.affiliation: 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.
authors.forename: Xiu Long
authors.initials: XL
authors.lastname: Niu
authors.affiliation: Department of Immunology, Logistics College of Chinese People's Armed Police Forces, Heping, Tianjin, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Wei Min
authors.initials: WM
authors.lastname: Deng
mesh_terms: D019898:Autocrine Communication / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C508598:IL4 protein, human; D013629:Tamoxifen; D015847:Interleukin-4; D007371:Interferon-gamma