TY - JOUR AB - In recent years, tumor necrosis factor receptor 2 (TNFR2) has attracted increasing attention for its important roles in promoting proliferation, migration and angiogenesis in several types of cancer. However, its role in drug resistance remain unclear. In the present study, TNFR2 expression levels in MDA‑MB‑231 and MCF‑7 breast cancer cells were demonstrated to be associated with Adriamycin (ADM) resistance. Silencing of TNFR2 in MCF‑7 cells significantly inhibited ADM resistance, while overexpression of TNFR2 in MDA‑MB‑231 cells significantly enhanced ADM resistance. ADM treatment induced phosphorylation of the histone family 2A variant X (pH2AX), an established marker of DNA damage. Silencing of TNFR2 in MCF‑7 cells further induced pH2AX levels but inhibited the expression of the DNA damage repair protein, poly(ADP‑ribose) polymerase (PARP). By contract, overexpression of TNFR2 in MDA‑MB‑231 cells decreased pH2AX levels and enhanced PARP expression. Of note, treatment with the PARP inhibitor ABT888 significantly abrogated the effects of TNFR2 on pH2AX expression. On a molecular mechanism level, TNFR2 significantly affected the phosphorylation of AKT serine/threonine kinase 1 (AKT) in both cell lines, and treatment with the AKT inhibitor LY294002 effectively abrogated TNFR2‑induced PARP expression. A drug resistance assay demonstrated that treatment with either LY294002 or ABT888 inhibited ADM resistance in breast cancer cells, and combination treatment with both LY294002 and ABT888 exhibited a significantly stronger inhibition effect on ADM resistance. The present results indicated that TNFR2 promoted ADM resistance in breast cancer cells by regulating the DNA damage repair protein PARP via the AKT signaling pathway. AD - Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China Medical Examination Center, Fangzi People's Hospital, Weifang, Shandong 261000, P.R. China AU - Yang,Fuqian AU - Zhao,Nana AU - Wu,Nan DA - 2017/09/01 DO - 10.3892/mmr.2017.6898 EP - 2968 IS - 3 JO - Mol Med Rep KW - tumor necrosis factor receptor 2 breast cancer Adriamycin phosphorylated histone family 2A variant X poly(ADP‑ribose) polymerase PY - 2017 SN - 1791-2997 1791-3004 SP - 2962 ST - TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage T2 - Molecular Medicine Reports TI - TNFR2 promotes Adriamycin resistance in breast cancer cells by repairing DNA damage UR - https://doi.org/10.3892/mmr.2017.6898 VL - 16 ER -