Human uroplakin lb gene structure and promoter analysis.
The uroplakin Ib (UPIb) gene is predominantly expressed in urothelium and is overexpressed in 50% of transitional cell carcinoma (TCC). Molecular cloning of the genomic 5' region and comparison to a chromosome 3q genomic contig determined that the gene spans 31 kb and has eight exons including a noncoding exon 1. Multiple transcription start sites were identified in exon 1 by 5'RACE and ribonuclease protection assay (RPA). In vitro reporter gene analysis was performed with 2.3 kb of genomic DNA sequence flanking the 5' end of UPIb. A 235-bp 5' fragment that included UPIb exon 1 generated strong transcriptional activity in normal and malignant human urothelial cell lines. Established malignant cell lines had greater transcriptional activity from the UPIb promoter than normal human cells. The identification of a functional human UPIb gene promoter may find application in targeting gene therapy strategies for bladder cancer.
Olsburgh
Jonathon
J
ICRF Cancer Research Centre, Leeds, UK.
Weeks
Robert
R
Selby
Peter
P
Southgate
Jennifer
J
D020121:5' Untranslated Regions / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000737:chemistry; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012313:RNA / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured; D060169:Uroplakin Ib; D019459:Urothelium / Q000378:metabolism*
D020121:5' Untranslated Regions; D008562:Membrane Glycoproteins; C086452:UPK1B protein, human; D060169:Uroplakin Ib; D012313:RNA; D004247:DNA; D008156:Luciferases