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 urothelial cells. Normal urothelium expressed mRNA for all four uroplakins, although UPIII could be detected only by ribonuclease protection assay. By in situ hybridization, UPIa and UPII were confined to superficial cells and UPIb was also expressed by intermediate cells. Cultured normal human urothelial cells showed a proliferative basal/intermediate cell phenotype and constitutive expression of UPIb only. Uroplakin expression by transitional cell carcinoma cell lines was related to their differentiated phenotype in vitro. RT4 cells expressed all uroplakins, VM-CUB-3 expressed three uroplakins, RT112 and HT1376 cells expressed only UPIb in high abundance, and COLO232, KK47, and EJ cells had no detectable expression. These results correlated with patterns of uroplakin expression in tumors. UPIa and UPII were detected superficially only in well differentiated transitional cell carcinoma papillae. UPIb was positive in seven of nine and overexpressed in five of nine noninvasive transitional cell carcinomas and was also present in four of eight invasive transitional cell carcinomas. Lymph node metastases retained the same pattern of UPIb expression as the primary tumor. Unlike the three differentiation-regulated uroplakins, UPIb may have an alternative role in urothelial cell/tissue processes.
Lobban
E D
ED
ICRF Cancer Medicine Research Unit, St. James's University Hospital, Leeds, United Kingdom.
Smith
B A
BA
Hall
G D
GD
Harnden
P
P
Roberts
P
P
Selby
P J
PJ
Trejdosiewicz
L K
LK
Southgate
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014571:Urologic Neoplasms / Q000378:metabolism; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D019459:Urothelium / Q000378:metabolism*
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C086451:UPK1A protein, human; C086452:UPK1B protein, human; C554658:UPK2 protein, human; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib