Uroplakin gene expression in normal human tissues and locally advanced bladder cancer.
The uroplakins are widely regarded as urothelium-specific markers of terminal urothelial cytodifferentiation. This study investigated the expression of the four uroplakin genes, UPIa, UPIb, UPII and UPIII, in a wide range of normal human tissues to determine tissue specificity and in advanced transitional cell carcinoma (TCC) to examine gene expression in primary and metastatic disease. In the urinary tract, all four uroplakins were expressed by urothelium and UPIII was also expressed by prostatic glandular epithelium. UPIa and UPII appeared to be urothelium-specific, but UPIb was detected in several non-urothelial tissues, including the respiratory tract, where it was associated with squamous metaplasia of tracheal and bronchial epithelia. The ten cases of primary TCC and corresponding lymph node metastases demonstrated that each uroplakin gene could be expressed at the mRNA level. No single uroplakin gene was expressed in all primary tumours or metastases, but 80% of the primary tumours and 70% of the lymph node metastases expressed at least one uroplakin gene. UPIII mRNA was often expressed in the absence of UPIII protein. These results confirm that in human tissues the expression of UPIa and UPII genes is highly specific to urothelium and suggest that the tight differentiation-restricted expression of uroplakin genes in normal urothelium is lost following malignant transformation.
Olsburgh
Jonathon
J
Imperial Cancer Research Fund Clinical Centre, Leeds, UK.
Harnden
Patricia
P
Weeks
Robert
R
Smith
Barbara
B
Joyce
Adrian
A
Hall
Geoffrey
G
Poulsom
Richard
R
Selby
Peter
P
Southgate
Jennifer
J
D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D001743:Urinary Bladder / Q000503:physiopathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D019459:Urothelium / Q000502:physiology
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C086451:UPK1A protein, human; C086452:UPK1B protein, human; C554658:UPK2 protein, human; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D012313:RNA