Publication
Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer
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- Persistent URL
- Last modified
- 03/03/2025
- Type of Material
- Authors
- Language
- English
- Date
- 2017-04-28
- Publisher
- Frontiers Media
- Publication Version
- Copyright Statement
- © 2017 Hou, Alemozaffar, Yang, Sands, Kong and Chen.
- License
- Final Published Version (URL)
- Title of Journal or Parent Work
- ISSN
- 1664-042X
- Volume
- 8
- Start Page
- 245
- End Page
- 245
- Grant/Funding Information
- Ruida Hou was supported by the China Scholarship Council (CSC) under the State Scholarship Fund.
- This work was supported by Emory URC grant (to GC) and NIH grants R01-DK087838 (to GC), and R01-DK89828 and R01-DK41707 (to JS)
- Abstract
- The urea transporter UT-B is widely expressed and has been studied in erythrocyte, kidney, brain and intestines. Interestingly, UT-B gene has been found more abundant in bladder than any other tissue. Recently, gene analyses demonstrate that SLC14A1 (UT-B) gene mutations are associated with bladder cancer, suggesting that urea transporter UT-B may play an important role in bladder carcinogenesis. In this study, we examined UT-B expression in bladder cancer with human primary bladder cancer tissues and cancer derived cell lines. Human UT-B has two isoforms. We found that normal bladder expresses long form of UT-B2 but was lost in 8 of 24 (33%) or significantly downregulated in 16 of 24 (67%) of primary bladder cancer patients. In contrast, the short form of UT-B1 lacking exon 3 was detected in 20 bladder cancer samples. Surprisingly, a 24-nt in-frame deletion in exon 4 in UT-B1 (UT-B1Δ24) was identified in 11 of 20 (55%) bladder tumors. This deletion caused a functional defect of UT-B1. Immunohistochemistry revealed that UT-B protein levels were significantly decreased in bladder cancers. Western blot analysis showed a weak UT-B band of 40 kDa in some tumors, consistent with UT-B1 gene expression detected by RT-PCR. Interestingly, bladder cancer associate UT-B1Δ24 was barely sialylated, reflecting impaired glycosylation of UT-B1 in bladder tumors. In conclusion, SLC14A1 gene and UT-B protein expression are significantly changed in bladder cancers. The aberrant UT-B expression may promote bladder cancer development or facilitate carcinogenesis induced by other carcinogens.
- Author Notes
- Keywords
- Research Categories
- Biology, Microbiology
- Health Sciences, Oncology
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