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

Document Type : Original Paper


1 Ionizing and Non-Ionizing Radiation Protection Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Radiology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Radiology, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences

4 Department of Radiology & Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran


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.


Main Subjects

  1. Da Silva L, Lakhani SR. Pathology of hereditary breast cancer. Modern Pathology. 2010 May 1;23:S46-51.
  2. Godet I, Gilkes DM. BRCA1 and BRCA2 mutations and treatment strategies for breast cancer. Integr Cancer Sci Ther. 2017; 4(1). DOI: 10.15761/ICST.1000228.
  3. Cortés C, Rivera AL, Trochez D, Solarte M, Gómez D, Cifuentes L, et al. Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia. Hereditary cancer in clinical practice. 2019 Dec;17(1):1-0.
  4. Van Der Groep P, Van Der Wall E, Van Diest PJ. Pathology of hereditary breast cancer. Cellular oncology. 2011 Apr;34:71-88.
  5. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease. The Lancet. 2001 Oct 27;358(9291):1389-99.
  6. Semmler L, Reiter-Brennan C, Klein A. BRCA1 and breast cancer: a review of the underlying mechanisms resulting in the tissue-specific tumorigenesis in mutation carriers. Journal of breast cancer. 2019 Mar 1;22(1):1-4.
  7. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nature Reviews Cancer. 2012 Jan;12(1):68-78.
  8. Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell. 2011 May 13;145(4):529-42.
  9. Jin TY, Park KS, Nam SE, Yoo YB, Park WS, Yun IJ. BRCA1/2 serves as a biomarker for poor prognosis in breast carcinoma. International Journal of Molecular Sciences. 2022 Mar 29;23(7):3754.
  10. Kan C, Zhang J. BRCA1 mutation: a predictive marker for radiation therapy?. International Journal of Radiation Oncology* Biology* Physics. 2015 Oct 1;93(2):281-93.
  11. Depuydt J, Viaene T, Blondeel P, Roche N, Van den Broecke R, Thierens H, et al. DNA double strand breaks induced by low dose mammography X‑rays in breast tissue: A pilot study. Oncology Letters. 2018 Sep 1;16(3):3394-400.
  12. Pereira L, Ferreira MT, Lima AG, Salata C, Ferreira-Machado SC, Lima I, et al. Biological effects induced by doses of mammographic screening. Physica Medica. 2021 Jul 1;87:90-8.
  13. Mills CE, Thome C, Koff D, Andrews DW, Boreham DR. The relative biological effectiveness of low-dose mammography quality X rays in the human breast MCF-10A cell line. Radiation Research. 2015 Jan 1;183(1):42-51.
  14. Fridlich R, Annamalai D, Roy R, Bernheim G, Powell SN. BRCA1 and BRCA2 protect against oxidative DNA damage converted into double-strand breaks during DNA replication. DNA repair. 2015 Jun 1;30:11-20.
  15. Mehrgou A, Akouchekian M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Medical journal of the Islamic Republic of Iran. 2016;30:369.
  16. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. The American Journal of Human Genetics. 2003 May 1;72(5):1117-30.
  17. Wang GH, Zhao CM, Huang Y, Wang W, Zhang S, Wang X. BRCA1 and BRCA2 expression patterns and prognostic significance in digestive system cancers. Human Pathology. 2018 Jan 1;71:135-44.
  18. Hatano Y, Tamada M, Matsuo M, Hara A. Molecular trajectory of BRCA1 and BRCA2 mutations. Frontiers in Oncology. 2020 Mar 25;10:361.
  19. De Talhouet S, Peron J, Vuilleumier A, Friedlaender A, Viassolo V, Ayme A, et al. Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. Scientific reports. 2020 Apr 27;10(1):7073.
  20. Zhao, L., C. Bao, Y. Shang, X. He, C. Ma, X. Lei, et al., The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks. Biomed Res Int, 2020. 2020: p. 4834965-77.
  21. Jeng YM, Cai-Ng S, Li A, Furuta S, Chew H, Chen PL, Lee EY,et al. Brca1 heterozygous mice have shortened life span and are prone to ovarian tumorigenesis with haploinsufficiency upon ionizing irradiation. Oncogene. 2007 Sep;26(42):6160-6.
  22. Zhu Y, Wu J, Zhang C, Sun S, Zhang J, Liu W, et al. BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis. Oncotarget. 2016 Oct 10;7(43):70113.
  23. Trainer AH, Lewis CR, Tucker K, Meiser B, Friedlander M, Ward RL. The role of BRCA mutation testing in determining breast cancer therapy. Nature reviews Clinical oncology. 2010 Dec;7(12):708-17.
  24. Templeton AJ, Gonzalez LD, Vera-Badillo FE, Tibau A, Goldstein R, Šeruga B, et al. Interaction between hormonal receptor status, age and survival in patients with BRCA1/2 germline mutations: a systematic review and meta-regression. PLoS One. 2016 May 5;11(5):e0154789.
  25. Chapman BV, Liu D, Shen Y, Olamigoke OO, Lakomy DS, Barrera AM, et al. Outcomes After Breast Radiation Therapy in a Diverse Patient Cohort With a Germline BRCA1/2 Mutation. International Journal of Radiation Oncology* Biology* Physics. 2022 Feb 1;112(2):426-36.