Methylation of a CpG Island within the Uroplakin Ib Promoter: A Possible Mechanism for Loss of Uroplakin lb Expression in Bladder Carcinoma

• DOI: 10.1593/neo.03337
• Publication Date: 2005-10-10T21:05:40Z
• Authors: Andrea E. Varga; Lefta Leonardos; Paul Jackson; Alexandra Marreiros; Prue A. Cowled
• Keywords: CpG site; Bisulfite sequencing

Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression uroplakin mRNA reduced or absent in many transitional cell carcinomas (TCCs) but molecular mechanisms underlying loss expression remain to be determined. Analysis promoter identified weak CpG island spanning proximal promoter, exon 1, and beginning intron 1. This study examined hypothesis that methylation this regulates expression. levels were determined by reverse transcription polymerase chain reaction was assessed bisulfite modification DNA, PCR, sequencing. A correlation demonstrated 15 TCC lines between lack methylation. In support regulatory role for methylation, incubating Ib-negative with 5-aza-2′ -deoxycytidine reactivated trend also observed normal urothelium bladder carcinomas. particular, correlated putative Spi/NFκB binding motif. The data are consistent specific sites within may an important factor TCCs.