Effect of RAD51C expression on the chemosensitivity of Eμ-Myc p19Arf-/- cells and its clinical significance in breast cancer

Abstract

The aim of the present study was to investigate the chemosensitivity to anti-cancer drugs of RAD51 paralog C (RAD51C)-deficient Eμ-Myc p19Arf-/- cells, to detect the expression of RAD51C in breast cancer tissues by immunohistochemistry (IHC), and to explore their association with clinicopathological factors. Eμ-Myc p19Arf-/- cells were stably transfected with retroviruses co-expressing short hairpin-RNA against RAD51C and green fluorescent protein (GFP). A single-cell flow cytometry-based GFP competition assay was used to assess the change in sensitivity to anti-cancer drugs. GFP-negative cells in the same population served as an internal control. In total, tissue samples from 213 cases of breast cancer and 99 adjacent non-cancerous tissue samples were collected to construct tissue microarrays. IHC was used to detect the expression of RAD51C protein. Relevant clinical information was collected for a correlation analysis. Transfection of RAD51C-shRNA was demonstrated to effectively reduce the RAD51C protein expression in the Eμ-Myc p19Arf-/- cells. The sensitivities of the cells to three drugs, camptothecin, cisplatin and olaparib, significantly increased following RAD51C gene knockdown. In breast cancer tissue, RAD51C expression was significantly higher in the Erb-B2 receptor tyrosine kinase 2 overexpression group. The overall survival time of the patients with RAD51C-negative expression was longer than that of patients with RAD51C-positive expression. RAD51C expression was an independent prognostic factor for survival of breast cancer patients. In summary, the results indicate that silencing of RAD51C may represent a potential therapeutic strategy for malignant tumors, and that measuring RAD51C expression by IHC may have prognostic value for breast cancer patients.