Role of Calcium in an Experimental Breast Cancer Model Induced by Radiation and Estrogen

Abstract

Background: Breast cancer, a global health challenge, significantly impacts women worldwide, causing morbidity, disability, and mortality. Objectives: To analyze the role of genes encoding S100 calcium-binding proteins and their relationship with radiation as possible markers in breast carcinogenesis. Methods: The normal MCF-10F cell line was used to study the role of ionizing radiation and estrogen to induce distinct stages of malignancy giving rise to an in vitro experimental breast cancer model. Results: Analysis of an Affymetrix system revealed that the gene expression levels of the S100 calcium-binding protein P (S100P), the S100 calcium-binding protein A14 (S100A14), and the S100 calcium-binding protein A2 (S100A2) were greater in the Tumor2 than the non-tumorigenic Alpha3 or the tumorigenic Alpha5 cell lines; however, the S100 calcium-binding protein A8 (S100A8) and the S100 calcium-binding protein A9 (S100A9) expression levels were higher in A5 than T2 and A3 cell lines. A significant positive association was found between the estrogen receptor alpha gene (ESR1) and S100A14 in Basal and Her2 patients. The association between ESR1 and S100A8 and S100A9 expression levels was positive in Basal patients but negative in Her2, Luminal A, and Luminal B. S100P and S100A14 expression levels were higher in tumor tissues than in normal ones. The estrogen receptor status was positive in patients with high levels of the S10014 gene, but negative in S100A2, S100A8, and S100A9 expression levels. Conclusion: Cell dependence needs to be considered while designing new breast cancer treatments since gene signatures might vary depending on the type of tumor.

Keywords

• S100 proteins
• Ca²⁺-dependent signaling
• biomarkers
• estrogen
• breast cancer
• radiation