Disease relevance of UPK1B

• 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 [1].
• Lymph node metastases retained the same pattern of UPIb expression as the primary tumor [1].
• 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 [2].
• As in bladder epithelium, uroplakin Ib may protect the ocular surface from bacterial infection [3].
• A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas [4].

High impact information on UPK1B

• Human UPIa contained exclusively high mannose glycans, and human UPIb contained only complex glycans [5].
• Using a sensitive approach that combines in-gel glycosidase and protease digestions, permethylation of released glycans, and mass spectrometry, we have elucidated for the first time the native glycoform structures of the mouse UPIa receptor and those of its non-binding homolog, UPIb, and have determined the glycosylation site occupancy [5].
• In mammals, UPIII is forming a complex with a tetraspanin molecule uroplakin Ib [6].
• Cultured normal human urothelial cells showed a proliferative basal/intermediate cell phenotype and constitutive expression of UPIb only [1].
• Two high-affinity activators of PPARgamma, troglitazone (TZ) and rosiglitazone (RZ) induced the expression of mRNA for UPII and UPIb and, to a lesser extent, UPIa [7].

Biological context of UPK1B

• Using polymerase-chain-reaction techniques, we have cloned a partial human UPK1B cDNA which codes for the putative full open reading frame for the UPK1B protein [8].
• METHODS: The full-length cDNA of human uroplakin Ib was isolated from a cDNA library of human corneal epithelium, and the expression of uroplakin Ib in various tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR) [3].
• In vitro reporter gene analysis was performed with 2.3 kb of genomic DNA sequence flanking the 5' end of UPIb [9].
• In particular, loss of uroplakin Ib expression correlated with methylation of a putative Sp1/NFkappaB binding motif [4].
• Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing [4].

Anatomical context of UPK1B

• However, expression of UPK1B mRNA was undetectable or markedly reduced in 11 out of 16 samples of transitional-cell-bladder-carcinoma tissue and in all 5 bladder-carcinoma cell lines when compared with normal urothelial tissue [8].
• Using Northern analysis, we show that the human UPK1B gene is highly expressed in normal human urothelium [8].
• Human uroplakin Ib in ocular surface epithelium [3].
• RT-PCR detected uroplakin Ib in cornea, conjunctiva, bladder, placenta, and kidney [3].
• Immunofluorescence confocal microscopy documented uroplakin Ib protein in the cell membranes of superficial and wing cells in the corneal epithelium [3].

Associations of UPK1B with chemical compounds

• In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2'-deoxycytidine reactivated uroplakin Ib mRNA expression [4].

Regulatory relationships of UPK1B

• This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression [4].

Other interactions of UPK1B

• Chromosomal localization of the human urothelial "tetraspan" gene, UPK1B, to 3q13.3-q21 and detection of a TaqI polymorphism [10].
• The combination of UPIb/UPIII was the most specific (79%) but had modest sensitivity (31%) [11].
• Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1 [4].

Analytical, diagnostic and therapeutic context of UPK1B

• By in situ hybridization, UPIa and UPII were confined to superficial cells and UPIb was also expressed by intermediate cells [1].
• Finally, the localization of uroplakin Ib in the ocular surface was analyzed by immunofluorescence confocal microscopy, by using an antiserum against a synthetic peptide [3].
• The identification of a functional human UPIb gene promoter may find application in targeting gene therapy strategies for bladder cancer [9].
• By immunohistochemistry, we found that in 15/18 cases of human ureter, but in only 2/10 cases of bladder, groups of normal-looking, CK18-positive umbrella cells lacked both UPIII and UPIb immunostaining [12].

References