comparable molecular alterations in 4nitroquinoline 1oxideinduced oral and esophageal cancer in mice and in human esophageal cancer associated with poor prognosis of patients background the murine model of 4nitroquinoline 1oxide 4nqoinduced oral and esophageal cancer is frequently used to assess the effects of different cancer prevention therapy agents in vivo but the molecular mechanisms in those 4nqoinduced carcinogenesis are unknown this study investigated aberrant expression of cell growthcritical genes in 4nqoinduced oral and esophageal cancer tissues in mice compared to those present in the human disease for association with survival of patientsmaterials and methods c57lb6129sv mice were given 4nqo in their drinking water to induce oral and esophageal cancer quantitativereverse transcription polymerase chain reaction qrtpcr western blot and immunohistochemistry were used to detect gene expression in the cancer tissues from mice and in 4nqotreated human esophageal cancer cell lines and esophageal cancer tissues methylationspecific pcr and dna sequencing were performed to assess methylation of the rarb2 promoter in murine tissues kaplanmeier analysis was performed to associate gene expression in esophageal cancer tissues with survival data for patients with esophageal cancerresults 4nqo dosedependently induced premalignant and malignant lesions in the oral cavity and esophagus in mice that pathologically and morphologically mimicked human oral and esophageal cancer molecularly 4nqo inhibited rar2 but induced expression of phosphorylated extracellularsignalregulated kinase1 and 2 perk12 and cox2 proteins and rar2 gene promoter methylation in murine tumors in vitro treatment with 4nqo altered expression of rar2 perk12 and cox2 in human esophageal cancer cells in tissues from 90 patients with esophageal cancer expression of perk12 and cox2 was upregulated and perk12 expression was associated with advanced clinical tumor stage and consumption of hot beverages while cox2 expression was associated with tumor dedifferentiation in esophageal cancer furthermore expression of perk12 was associated with a worse overall survival rate of patients p0014 whereas the association of cox2 expression with worse overall survival rate did not reach statistical significance p019 knockdown of cox2 expression using transient transfection of a cox2 antisense expression vector inhibited ki67 expression an indicator of cell proliferation in human esophageal cancer cellsconclusion 4nqoinduced cancer in oral cavity and esophagus of mice not only pathologically and morphologically mimicked human oral and esophageal cancer but also shared some molecular alterations eg aberrant expression of rarb2 perk12 and cox2 this study further demonstrated that targeting of the altered rar2led gene pathway could effectively suppress the development of this deadly type of cancer