FoxO3a gene is a target of deletion in mouse lung adenocarcinoma

摘要: Lung adenocarcinomas (LAC) of smokers and never-smokers differ from one another in epidemiology, clinical molecular characteristics. The pathogenetic differences between these tumors are potential biomarkers therapeutic targets. Mouse carcinogenesis models human LAC proven tools applicable for the identification changes. Allelic loss frequency on chromosome 6q is higher compared with never smokers. We analyzed orthologous region mouse 10 found this similarly was a more frequent site allelic carcinogen-induced non-induced or spontaneous LAC. then conducted high resolution quantitative PCR-based deletion mapping identified FoxO3a gene as focus bi-allelic homozygous (HD). HDs were detected 5 out 15 (33.3%) cell lines 6 75 (8%) primary exclusively affected by HD 7 samples examined, both alleles did extend to nearest flanking genes FoxO3a. Deletion FoxO3a, either subclonal 38 (50.7%) contrast only 1 (10%) untreated mice. Several also subjected direct sequence analysis; however, no intragenic mutations detected. These results implicate selective target Significant association carcinogenic induction suggests that contributes development carcinogen-initiated tumors.