Gene expression in normal Urothelium depends on location within the bladder: A possible link to bladder carcinogenesis

Sharon C Doherty, SR McKeown, Jesus A Lopez, Ian K Walsh, Valerie J McKelvey-Martin

    Research output: Contribution to journalArticle

    Abstract

    Objectives: Clinical studies have shown that more than 70% of primary bladder tumours arise in the area around the ureteric orifice. In this study a genomic approach was taken to explore the molecular mechanisms that may influence this phenomenon. Methods: RNA was isolated from each individual normal ureteric orifice and the dome biopsy from 33 male patients. Equal amounts of the pooled ureteric orifice and dome mRNAs were labelled with Cy3 and Cy5, respectively before hybridising to the gene chip (UniGEM 2.0, Incyte Genomics Inc., Wilmington, Delaware, USA). Results: Significant changes (more than a twofold difference) in gene expression were observed in 3.1% (312) of the 10,176 gene array: 211 genes upregulated and 101 downregulated. Analysis of Cdc25B, TK1, PKM, and PDGFra with RT-PCR supported the reliability of the microarray result. Seladin-1 was the most upregulated gene in the ureteric orifice: 8.3-fold on the microarray and 11.4-fold by real time PCR. Conclusions: Overall, this study suggests significant altered gene expression between these two anatomically distinct areas of the normal human bladder. Of particular note is Seladin-1, whose significance in cancer is yet to be clarified. Further studies of the genes discovered by this work will help clarify which of these differences influence primary bladder carcinogenesis. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    LanguageEnglish
    Pages290-301
    JournalEuropean Urology
    Volume50
    Issue number2
    DOIs
    Publication statusPublished - Aug 2006

    Fingerprint

    Urothelium
    Carcinogenesis
    Urinary Bladder
    Gene Expression
    Genes
    Genomics
    Oligonucleotide Array Sequence Analysis
    Urinary Bladder Neoplasms
    Reproducibility of Results
    Real-Time Polymerase Chain Reaction
    Down-Regulation
    RNA
    Biopsy
    Polymerase Chain Reaction
    Messenger RNA
    Neoplasms

    Keywords

    • normal bladder
    • gene expression
    • microarray
    • Seladin-1

    Cite this

    Doherty, Sharon C ; McKeown, SR ; Lopez, Jesus A ; Walsh, Ian K ; McKelvey-Martin, Valerie J. / Gene expression in normal Urothelium depends on location within the bladder: A possible link to bladder carcinogenesis. In: European Urology. 2006 ; Vol. 50, No. 2. pp. 290-301.
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    Gene expression in normal Urothelium depends on location within the bladder: A possible link to bladder carcinogenesis. / Doherty, Sharon C; McKeown, SR; Lopez, Jesus A; Walsh, Ian K; McKelvey-Martin, Valerie J.

    In: European Urology, Vol. 50, No. 2, 08.2006, p. 290-301.

    Research output: Contribution to journalArticle

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    AU - McKeown, SR

    AU - Lopez, Jesus A

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    AU - McKelvey-Martin, Valerie J

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