title: Ku80 is differentially expressed in human lung carcinomas and upregulated in response to irradiation in mice.
abstract: Based on the role of Ku80 in mediating radiation-induced DNA repair, we investigated Ku80 expression in human lung cancers of different pathological types and evaluated the effect of radiotherapy on Ku80 expression levels in a mouse model. We used immunohistochemistry and real-time PCR to determine Ku80 protein and mRNA levels, respectively. We inoculated nude mice with A549 cells and subjected the tumor-bearing mice to varying doses of irradiation. Lung carcinoma tissue exhibited higher Ku80 mRNA and protein levels when compared with normal tissue. Among the tumor subtypes, lung adenocarcinoma and lung squamous carcinoma showed higher levels of Ku80 protein and mRNA, compared with small-cell lung carcinoma. There was a dose-dependent and time-dependent increase in Ku80 mRNA levels in nude mice that were inoculated with A549 cells and exposed to varying doses of irradiation. Ku80 may play an important role in the DNA damage response pathway. Higher Ku80 levels in lung squamous carcinoma and adenocarcinoma may explain their lower radiosensitivity when compared with small-cell lung carcinoma. Ku80 expression levels could be useful in predicting radiosensitivity of lung tumors and inhibition of Ku80 may be an interesting target to improve radiosensitivity in lung cancer patients.
authors.affiliation: Department of Pneumology, The First People's Hospital, Hangzhou, China. jianye17@126.com
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Ren
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D034961:Antigens, Nuclear / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000637:transplantation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D000072200:Ku Autoantigen; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D013047:Specific Pathogen-Free Organisms
chemical_list: D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen