Takashi Kobunai1, Toshiaki Watanabe, Toshio Fukusato. 1. Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. azteca_tk@yahoo.co.jp
Abstract
AIM: The present study aimed to identify genes that influence the susceptibility of cancer cells to radiation. MATERIALS AND METHODS: The sensitivities of eight colorectal cancer cell lines to gamma radiation were tested. Microarray data and cells with stable overexpression were used to identify candidate genes. Candidate genes correlating with radioresistance were validated with the use of 22 clinical specimens obtained before preoperative radiotherapy from patients with rectal cancer. RESULTS: Regenerating islet-derived protein 4 (REG4) gene expression was 12-fold higher in radioresistant cells. REG4-overexpressing cells had higher survival rates and fewer DNA strand breaks after gamma irradiation. Expression of the antiapoptotic gene baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and base excision-repair pathway gene nei endonuclease VIII-like 2 (NEIL2) in REG4-overexpressing cells, was also three to four times higher than that of the parental cell lines. REG4, BIRC5 and NEIL2 expression levels were significantly higher in non-responding patients (n=14) than in responders (n=8). CONCLUSION: The REG4, BIRC5 and NEIL2 genes might be useful predictors of the sensitivity of cancer patients to radiotherapy.
AIM: The present study aimed to identify genes that influence the susceptibility of cancer cells to radiation. MATERIALS AND METHODS: The sensitivities of eight colorectal cancer cell lines to gamma radiation were tested. Microarray data and cells with stable overexpression were used to identify candidate genes. Candidate genes correlating with radioresistance were validated with the use of 22 clinical specimens obtained before preoperative radiotherapy from patients with rectal cancer. RESULTS:Regenerating islet-derived protein 4 (REG4) gene expression was 12-fold higher in radioresistant cells. REG4-overexpressing cells had higher survival rates and fewer DNA strand breaks after gamma irradiation. Expression of the antiapoptotic gene baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and base excision-repair pathway gene nei endonuclease VIII-like 2 (NEIL2) in REG4-overexpressing cells, was also three to four times higher than that of the parental cell lines. REG4, BIRC5 and NEIL2 expression levels were significantly higher in non-responding patients (n=14) than in responders (n=8). CONCLUSION: The REG4, BIRC5 and NEIL2 genes might be useful predictors of the sensitivity of cancerpatients to radiotherapy.
Authors: Renuka R Nayak; William E Bernal; Jessica W Lee; Michael J Kearns; Vivian G Cheung Journal: Nucleic Acids Res Date: 2013-10-28 Impact factor: 16.971