Disease relevance of UPK2

• UPIa and UPII were detected superficially only in well differentiated transitional cell carcinoma papillae [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].
• Identification of human uroplakin II promoter and its use in the construction of CG8840, a urothelium-specific adenovirus variant that eliminates established bladder tumors in combination with docetaxel [3].
• The specific and sensitive detection of uroplakin II provides a useful adjunct for detecting bladder cancer metastasis, staging, and monitoring chemotherapeutic response [4].
• Mice with null mutation of another UP family member, UPII, are often born with congenital hydronephrosis [5].

High impact information on UPK2

• At the amino terminus, residues 39 to 54 are highly homologous to a peptide in calf thymus UP1 and UP2 and a human heterogeneous nuclear ribonucleoprotein [6].
• UPII gene expression is bladder specific and differentiation dependent, but very little is known about its transcription response elements [3].
• To identify the promoter elements, a DNA fragment of 2239 bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene [3].
• We have developed a transgenic mouse model of bladder tumorigenesis using a 3.6-kb promoter of uroplakin II gene to drive the urotheliums-specific expression of oncogenes [7].
• Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation [8].

Biological context of UPK2

• Genes for uroplakins IA, IB, and II were mapped to bovine (BTA) Chromosomes (Chrs) 18 (UPK1A), 1 (UPK1B), and 15 (UPK2), respectively [9].
• The DNA-deduced amino acid sequences of bovine and mouse uroplakin II revealed 83% identity [10].
• In this study, we examine the mammalian uroplakins (UPs) Ia and Ib, members of the tetraspanin superfamily, that interact with uroplakins UPII and UPIIIa/IIIb, respectively, using a phylogenetic approach of these genes from whole genome sequences [11].
• PURPOSE: The nested reverse transcription polymerase chain reaction (RT-PCR) method was used to determine expression of uroplakin II (UP II) or cytokeratin 20 (CK-20) in cells separated from the peripheral blood of patients with urothelial cancer [12].
• METHODS: Mutations were sought, using direct sequencing of the five UPII exons, in 42 children with diverse renal tract anomalies [5].

Anatomical context of UPK2

• Among other uroplakins, uroplakin II was also faintly detected in cornea and conjunctiva [13].
• 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 [2].
• All patients with pathologically positive nodes had positive UPII signals in the lymph node sample [14].
• Uroplakin II (UPII) gene expression is highly tissue and cell specific, with mRNA present in the suprabasal cell layers of the bladder and urethra [15].
• However, deleting the 3' end 143-bp of the UPII promoter, the activity was hardly detected in any tissue cell lines [16].

Associations of UPK2 with chemical compounds

• 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 [17].
• Furthermore, neither 15d-PGJ2 nor PGJ2 were able to induce expression of the UPII gene in NHU cells, in contrast to cultures exposed to the pharmacologic PPAR-gamma agonist, troglitazone [18].

Other interactions of UPK2

• Detection of EGFR-positive cells alone and in combination with UPs was inferior to that for UPIa/UPII [19].
• Specifically, only uroplakin II (UP-II) and cytokeratin 20 (CK-20) have been suggested as tumor markers in the blood of bladder cancer patients [20].
• Detection of micrometastases in pelvic lymph nodes in patients undergoing radical cystectomy for locally invasive bladder cancer by real-time reverse transcriptase-PCR for cytokeratin 19 and uroplakin II [21].
• MATERIALS AND METHODS: Total RNAs were extracted from peripheral blood of 60 patients with TCC (50 non-metastatic and 10 metastatic) and 10 healthy controls, reverse-transcribed and subjected to polymerase chain reaction amplification (RT-PCR) using oligonucleotide primers of human uroplakin II gene [4].
• Intravesical inoculation with Ad-hUPII-TNF inhibited tumor growth in the orthotopic human bladder cancer model [22].

Analytical, diagnostic and therapeutic context of UPK2

• RT-PCR analysis for UPII mRNA was carried out on these biopsy specimens, and results were compared with data obtained from conventional pathological examination [14].
• UPII mRNA was detected in the blood samples of 2 patients with metastatic bladder cancer without chemotherapy and 1 out of 8 such patients with chemotherapy, but not in those of 50 non-metastatic patients or normal controls [4].
• To investigate the feasibility of targeting gene therapy for bladder cancer, a DNA fragment of 2542-bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene [22].
• Cloning and molecular dissection of the 8.8 kb pig uroplakin II promoter using transgenic mice and RT4 cells [15].
• To clone Uroplakin Ii gene from Chinese transitional cell carcinoma (TCC) of bladder and construct its eukaryotic expression vector, the molecular cloning method was used to extract total RNA from a GIII / T3N0M0 tissue sample of the bladder TCC patients [23].

References