Calaf Gloria M, Roy Debasish, Jara Lilian, Romero Carmen, Crispin Leodan A
Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile.
Department of Natural Sciences, Hostos College of the City University of New York, Bronx, NY 10451, USA.
Biology (Basel). 2024 Dec 20;13(12):1078. doi: 10.3390/biology13121078.
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.
乳腺癌是一个全球性的健康问题,在转移阶段,其特征是缺乏雌激素受体-α、孕激素受体和人表皮生长受体表达。本研究分析了先前建立的实验性乳腺癌模型衍生的细胞系中,与受电离辐射和雌激素影响的免疫系统相关的差异基因表达;将永生化人乳腺上皮细胞系MCF-10F(一种三阴性乳腺癌细胞系)暴露于低剂量的高线性能量转移α粒子辐射(150 keV/μm),随后在有或没有17β-雌二醇的情况下生长。结果表明,雌激素处理的细胞系中干扰素相关发育调节因子1基因表达受到影响;在Alpha3细胞系中,这种干扰素以及干扰素诱导跨膜蛋白2和肿瘤坏死因子α诱导蛋白6的基因表达水平高于对照组。此外,干扰素相关发育调节因子1、干扰素诱导跨膜蛋白2、肿瘤坏死因子α诱导蛋白6、核因子白细胞介素3调节因子和干扰素γ受体1在Alpha5细胞系中表达水平较高,而干扰素调节因子6在Tumor2细胞系中表达较高。此外,为了进一步强化这些数据,还分析了公开可用的数据集。进行该分析是为了评估乳腺癌患者中雌激素受体α表达与上述基因之间的相关性、肿瘤组织与正常组织之间的差异基因表达、免疫浸润水平、雌激素受体状态以及经临床分期因素调整后的生存结果。可以得出结论,干扰素家族基因和肿瘤坏死因子可成为乳腺癌的潜在治疗靶点,因为它们在肿瘤形成前就作为机体在辐射或雌激素作用下的防御机制而发挥作用。