Gefitinib-related gene signature in bladder cancer cells identified by a cDNA microarray.

BACKGROUND The aim of this study was to identify key genes linked to the molecular action of gefitinib, a promising anticancer agent on human bladder cancer cell lines. MATERIALS AND METHODS cDNA microarrays were used to profile feature genes in 5637 and T24 cells before and after treatment with gefitinib. PCR-based direct sequencing and Western blot analysis were performed to examine the mutation status and protein levels of EGFR in the cell lines. RESULTS Gefitinib significantly inhibited the proliferation of 5637 cells, while showing little inhibitory effect on T24 cells. Theses effects were independent of the mutation status and protein levels of EGFR. cDNA microarray analysis identified 15 feature genes classified as a cell cycle, apoptotic pathway and transcription. Notably, levels of expression of the cell invasion-related genes, YY1 and E-cadherin, were increased in 5637 cells sensitive to gefitinib. CONCLUSION Unique genes involved in the action of gefitinib were identified. Particularly, the upregulation of YY1 and E-cadherin may account for the efficacy of gefitinib in bladder cancer.