Gene expression in normal urothelium depends on location within the bladder: a possible link to bladder carcinogenesis.
OBJECTIVE
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.
Doherty
Sharon C
SC
Cancer and Ageing Research Group, Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, UK BT52 1SA. sc.doherty@ulster.ac.uk
McKeown
Stephanie R
SR
Lopez
Jesus A
JA
Walsh
Ian K
IK
McKelvey-Martin
Valerie J
VJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics; D019459:Urothelium
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm