Gene Profiling of Cyclosporin-Enhanced Transitional Cell Carcinoma in Rat Model

ObjectiveWe sought to study the effect of cyclosporine (CsA) on development of malignancy.Materials and MethodsThe observation was performed in a rat model, in which transitional cell carcinoma of urinary bladder was induced with N-butyl-N-(-4-hydroxybutyl) nitrosamine. CsA was added in the food for the rats. At the end of 30 weeks, we examined the tumor burden in the urinary bladders, and compared gene expressions between the CsA-enhanced and non–CsA-enhanced tumor groups by gene profiling.ResultsCsA feeding increased tumor burden: 2.3 ± 0.9 versus 1.1 ± 0.5 g (P < .05). Gene profiling showed many variations involved in CsA enhanced malignant development. Twenty-three genes with known functions were upregulated, and 46 genes with known functions downregulated. In all, 111 genes were involved in the CsA-enhanced malignant development. The regulated genes in the present study constituted 23 pathways mostly involved in carcinogenesis.ConclusionsCsA plays an important role in tumor development through gene regulation, which may constitute pathways to malignant progression.