Methylation of a CpG island within the uroplakin lb promoter: A possible mechanism for loss of uroplakin lb expression in bladder carcinoma

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dc.contributor.authorVarga, A.
dc.contributor.authorLeondardos, L.
dc.contributor.authorJackson, P.
dc.contributor.authorMarreiros, A.
dc.contributor.authorCowled, P.
dc.date.issued2004
dc.description.abstractUroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs) but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1. This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing. A correlation was demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG methylation. In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2'-deoxycytidine reactivated uroplakin Ib mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas. In particular, loss of uroplakin Ib expression correlated with methylation of a putative Sp1/NFkappaB binding motif. The data are consistent with the hypothesis that methylation of specific sites within the uroplakin Ib promoter may be an important factor in the loss of uroplakin Ib expression in TCCs.
dc.description.statementofresponsibilityAndrea E Varga, Lefta Leonardos, Paul Jackson, Alexandra Marreiros, Prue A Cowled
dc.identifier.citationNeoplasia: An International Journal for Oncology Research, 2004; 6(2):128-135
dc.identifier.doi10.1593/neo.03337
dc.identifier.issn1522-8002
dc.identifier.issn1476-5586
dc.identifier.orcidCowled, P. [0000-0002-4533-6320]
dc.identifier.urihttp://hdl.handle.net/2440/10444
dc.language.isoen
dc.publisherNature America Inc
dc.source.urihttps://doi.org/10.1593/neo.03337
dc.subjectUrothelium
dc.subjectTumor Cells, Cultured
dc.subjectHumans
dc.subjectAzacitidine
dc.subjectDNA Modification Methylases
dc.subjectMembrane Glycoproteins
dc.subjectEnzyme Inhibitors
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectDNA Methylation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectBase Sequence
dc.subjectCpG Islands
dc.subjectMolecular Sequence Data
dc.subjectUrinary Bladder Neoplasms
dc.subjectPromoter Regions, Genetic
dc.subjectUroplakin Ib
dc.subjectDecitabine
dc.titleMethylation of a CpG island within the uroplakin lb promoter: A possible mechanism for loss of uroplakin lb expression in bladder carcinoma
dc.typeJournal article
pubs.publication-statusPublished

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