Genes Associated with the Immune System Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model

Abstract

Breast cancer is a global health issue that, when in the metastasis stage, is characterized by the lack of estrogen receptor-α, the progesterone receptor, and human epidermal growth receptor expressions. The present study analyzed the differential gene expression related to the immune system affected by ionizing radiation and estrogen in cell lines derived from an experimental breast cancer model that was previously developed; where the immortalized human breast epithelial cell line MCF-10F, a triple-negative breast cancer cell line, was exposed to low doses of high linear energy transfer α particle radiation (150 keV/μm), it subsequently grew in the presence or absence of 17β-estradiol. Results indicated that interferon-related developmental regulator 1 gene expression was affected in the estrogen-treated cell line; this interferon, as well as the Interferon-Induced Transmembrane protein 2, and the TNF alpha-induced Protein 6 gene expression levels were higher than the control in the Alpha3 cell line. Furthermore, the interferon-related developmental regulator 1, the Interferon-Induced Transmembrane protein 2, the TNF alpha-induced Protein 6, the Nuclear Factor Interleukin 3-regulated, and the Interferon-Gamma Receptor 1 showed high expression levels in the Alpha5 cell line, and the Interferon Regulatory Factor 6 was high in the Tumor2 cell line. Additionally, to further strengthen these data, publicly available datasets were analyzed. This analysis was conducted to assess the correlation between estrogen receptor alpha expression and the genes mentioned above in breast cancer patients, the differential gene expression between tumor and normal tissues, the immune infiltration level, the ER status, and the survival outcome adjusted by the clinical stage factor. It can be concluded that the genes of the interferon family and Tumor Necrosis factors can be potential therapeutic targets for breast cancer, since they are active before tumor formation as a defense of the body under radiation or estrogen effects.