Effect of Dose Irradiation on the Expression of BRCA1 and BRCA2Genes in MCF-10A and MCF-7 cell lines

Abstract

Introduction: Breast cancer can be caused by a mutation in its genome. Some mutations are cancer-predisposition which exist at the moment of germ cell genesis. It has been discovered that BRCA1 and BRCA2 are linked to hereditary breast cancer. BRCA1/2 are tumor suppressor genes involved in DNA repair and transcriptional regulation in response to DNA damage. Irradiation, particularly ionizing radiation used in clinical radiotherapy, causes DNA damage. This study aims to find out whether different doses of x-radiation might change the expression of BRCA1/2. Material and Methods: Cancer and normal breast cell lines (MCF10-A and MCF7) cultured in flasks were irradiated with X- rays in different doses including 50, 100, 400, 2000, and 4000 mGy. Then, the expression of BRCA1/2 genes was measured using real-time quantitative reverse transcription PCR (RT-qPCR). Relative changes for mRNA were calculated based on the ∆∆Ct method. Results: MCF-10A cells represent a significant increase in BRCA2 expression at all irradiation doses while increasing the mRNA level for the BRCA1 gene observed after exposure to 50, 100, and 2000 mGy. This figure shows overexpression of BRCA2 gene after all irradiation doses except 100 mGy for MCF7 cells. The BRCA1 gene upregulated after exposure to 400 and 2000 mGy and downregulated at 50,100 and 4000 mGy in these cells. Conclusion: Incidence of cancer initiation was probable in normal breast cells after low-dose radiation, with up-regulation of BRCA1 and BRCA2 gene expression. BRCA mutation may be an inadequate outcome predictor of survival rate and other factors may be involved too.

Keywords

• brca1 brca2 mcf7 mcf
• 10a ionizing radiation