Effect of Dose Irradiation on the Expression of BRCA۱ and BRCA۲Genes in MCF-۱۰A and MCF-۷ cell lines

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 BRCA۱ and BRCA۲ are linked to hereditary breast cancer. BRCA۱/۲ 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 BRCA۱/۲. Material and Methods: Cancer and normal breast cell lines (MCF۱۰-A and MCF۷) cultured in flasks were irradiated with X- rays in different doses including ۵۰, ۱۰۰, ۴۰۰, ۲۰۰۰, and ۴۰۰۰ mGy. Then, the expression of BRCA۱/۲ 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-۱۰A cells represent a significant increase in BRCA۲ expression at all irradiation doses while increasing the mRNA level for the BRCA۱ gene observed after exposure to ۵۰, ۱۰۰, and ۲۰۰۰ mGy. This figure shows overexpression of BRCA۲ gene after all irradiation doses except ۱۰۰ mGy for MCF۷ cells. The BRCA۱ gene upregulated after exposure to ۴۰۰ and ۲۰۰۰ mGy and downregulated at ۵۰,۱۰۰ and ۴۰۰۰ mGy in these cells. Conclusion: Incidence of cancer initiation was probable in normal breast cells after low-dose radiation, with up-regulation of BRCA۱ and BRCA۲ gene expression. BRCA mutation may be an inadequate outcome predictor of survival rate and other factors may be involved too.

Keywords:

BRCA۱ BRCA۲ MCF۷ MCF , ۱۰A Ionizing Radiation