Uroplakin gene expression by normal and neoplastic human urothelium

cDNA sequences for human uroplakins UPIa, UPIb, UPII, and UPIII were cloned and used to investigate uroplakin transcription by normal and neoplastic u rothelial cells. Normal urothelium expressed mRNA for all four uroplakins, although UPIII could be detected only by ribonuclease protection assay. By irt situ hybridization, UPIa and UPII were confined to superficial cells an d UPIb was also expressed by intermediate cells. Cultured normal human urot helial cells showed a proliferative basal/intermediate cell phenotype and c onstitutive expression of UPIb only. Uroplakin expression by transitional c ell carcinoma cell Lines was related to their differentiated phenotype in v itro. RT4 cells expressed all uroplakins, VM-CUB-3 expressed three uroplaki ns, RT112 and HT1376 cells expressed only UPIb in high abundance, and COLO2 32, KK47, and EJ cells had no detectable expression. These results correlat ed with patterns of uroplakin expression in tumors. UPIa and UPII were dete cted superficially only in well differentiated transitional cell carcinoma papillae, UPIb was positive in seven of nine and overexpressed in five of n ine non-invasive transitional cell carcinomas and was also present in four of eight invasive transitional cell carcinomas. Lymph node metastases retai ned the same pattern of UPIb expression as the primary tumor. Unlike the th ree differentiation-regulated uroplakins, UPIb may have an alternative role in urothelial cell/tissue processes.