ATM mediates DAB2IP-deficient bladder cancer cell resistance to ionizing radiation through the p38MAPK and NF-κB signaling pathway

He,Hui; Chang,Rulve; Zhang,Tingting; Yang,Chen; Kong,Zhaolu

doi:10.3892/mmr.2017.6689

ATM mediates DAB2IP-deficient bladder cancer cell resistance to ionizing radiation through the p38MAPK and NF-κB signaling pathway

Authors:
- Hui He
- Rulve Chang
- Tingting Zhang
- Chen Yang
- Zhaolu Kong
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Affiliations: Department of Radiobiology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China
Published online on: June 6, 2017 https://doi.org/10.3892/mmr.2017.6689
Pages: 1216-1222
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although surgery remains the standard therapy for the treatment of bladder cancer (BCa), the data from previous clinical studies suggest that there is an increase in the number of patients with a preference for bladder preservation strategies, including radiotherapy, to improve their life quality. Our preliminary results showed that disabled homolog 2 interactive protein (DAB2IP), a putative tumor suppressor gene, is often downregulated in BCa with a radioresistant phenotype. Subsequent investigations revealed that elevated expression of ataxia‑telangiectasia mutated (ATM) induced by DAB2IP‑knockdown may be the key event in BCa cell resistance to ionizing radiation (IR). However, how ATM is involved in the survival of DAB2IP‑deficient cells exposed to IR remains to be fully elucidated. The present study knocked down the expression of ATM in DAB2IP‑deficient BCa cells using RNA interference technology. Activation of mitogen‑activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) signaling pathways were detected by western blot analysis and immunofluorescence assay, respectively. It was demonstrated that knockdown of ATM enhanced the response of DAB2IP‑deficient BCa cells to IR, which may have resulted from delayed DNA double‑strand break repair kinetics, compromised nuclear factor‑κB translocation, inhibited phosphorylation of p38 and the induced activation of c‑Jun N‑terminal kinase. Taken together, these findings suggested that ATM may be an effective target in the radiotherapy of patients with DAB2IP-deficient BCa.

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