CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer
Autor: | Yoram Cohen, Claus F. Eisenberger, Motonabu Osada, Zhongmin Guo, Lambertus A. Kiemeney, Sarel Halachmi, Paul S. Meltzer, Alexey Fomenkov, Chulso Moon, Jeffrey M. Trent, Sarah L. Anzick, William H. Westra, Kenji Okami, David Sidransky, Guojun Wu, Gabriel Steiner, Barry Trink, James M. Engles, Mohammad O. Hoque, Edward A. Ratovitski, Mark P. Schoenberg, Jurgen F. Linn |
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Rok vydání: | 2004 |
Předmět: |
Molecular Sequence Data
Chromosomes Human Pair 20 Translocation Breakpoint Fluorescent Antibody Technique Chromosomal translocation Biology General Biochemistry Genetics and Molecular Biology Germline Translocation Genetic Mice Downregulation and upregulation Determinants in Health and Disease [EBP 1] medicine Animals Humans Cloning Molecular In Situ Hybridization Fluorescence Molecular diagnosis prognosis and monitoring [UMCN 1.2] Bladder cancer Oncogene Cancer General Medicine Oncogenes medicine.disease Urokinase receptor Urinary Bladder Neoplasms Immunology Cancer research NIH 3T3 Cells |
Zdroj: | Nature Medicine, 10, 4, pp. 374-81 Nature Medicine, 10, 374-81 |
ISSN: | 1078-8956 |
Popis: | Contains fulltext : 57326.pdf (Publisher’s version ) (Closed access) Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers. |
Databáze: | OpenAIRE |
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