{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:55:50Z","timestamp":1789656950014,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T00:00:00Z","timestamp":1366070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Clinical resistance to gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in patients with lung cancer has been linked to acquisition of the T790M resistance mutation in activated\n                    <jats:italic>EGFR<\/jats:italic>\n                    or amplification of\n                    <jats:italic>MET<\/jats:italic>\n                    . Phosphatase and tensin homolog (\n                    <jats:italic>PTEN<\/jats:italic>\n                    ) loss has been recently reported as a gefitinib resistance mechanism in lung cancer. The aim of this study was to evaluate the efficacy of radiotherapy in non\u2010small\u2010cell lung cancer (NSCLC) with acquired gefitinib resistance caused by PTEN deficiency to suggest radiotherapy as an alternative to EGFR TKIs. PTEN deficient\u2010mediated gefitinib resistance was generated in HCC827 cells, an EGFR TKI sensitive NSCLC cell line, by PTEN knockdown with a lentiviral vector expressing short hairpin RNA\u2010targeting PTEN. The impact of PTEN knockdown on sensitivity to radiation in the presence or absence of PTEN downstream signaling inhibitors was investigated. PTEN knockdown conferred acquired resistance not only to gefitinib but also to radiation on HCC827 cells. mTOR inhibitors alone failed to reduce HCC827 cell viability, regardless of PTEN expression, but ameliorated PTEN knockdown\u2010induced radioresistance. PTEN knockdown\u2010mediated radioresistance was accompanied by repression of radiation\u2010induced cytotoxic autophagy, and treatment with mTOR inhibitors released the repression of cytotoxic autophagy to overcome PTEN knockdown\u2010induced radioresistance in HCC827 cells. These results suggest that inhibiting mTOR signaling could be an effective strategy to radiosensitize NSCLC harboring the\n                    <jats:italic>EGFR<\/jats:italic>\n                    activating mutation that acquires resistance to both TKIs and radiotherapy due to\n                    <jats:italic>PTEN<\/jats:italic>\n                    loss or inactivation mutations. J. Cell. Biochem. 114: 1248\u20131256, 2013. \u00a9 2012 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jcb.24465","type":"journal-article","created":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T20:35:38Z","timestamp":1354134938000},"page":"1248-1256","source":"Crossref","is-referenced-by-count":41,"title":["mTOR inhibitors radiosensitize PTEN\u2010deficient non\u2010small\u2010cell lung cancer cells harboring an\n                    <i>EGFR<\/i>\n                    activating mutation by inducing autophagy"],"prefix":"10.1002","volume":"114","author":[{"given":"Eun 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