A critical role for choline kinase-α in the aggressiveness of bladder carcinomas Journal Article
| Authors: | Hernando, E.; Sarmentero-Estrada, J.; Koppie, T.; Belda-Iniesta, C.; Ramírez De Molina, V.; Cejas, P.; Ozu, C.; Le, C.; Sánchez, J. J.; González-Barón, M.; Koutcher, J.; Cordon-Cardo, C.; Bochner, B. H.; Lacal, J. C.; De Molina, A. R. |
| Article Title: | A critical role for choline kinase-α in the aggressiveness of bladder carcinomas |
| Abstract: | Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-α (ChoKα) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKα show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKα plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKα is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models, including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoKα potentiate both tumor formation (P0.0001) and aggressiveness of the disease on different end points (P0.011). Accordingly, increased levels of ChoKα significantly reduce survival of mice with bladder cancer (P0.05). Finally, treatment with a ChoKα-specific inhibitor resulted in a significant inhibition of tumor growth (P0.02) and in a relevant increase in survival (P0.03). © 2009 Macmillan Publishers Limited All rights reserved. |
| Keywords: | cancer survival; controlled study; survival rate; unclassified drug; oncoprotein; human cell; cancer growth; nonhuman; antineoplastic agent; animal cell; mouse; animals; mice; animal tissue; mus; gene overexpression; animal experiment; animal model; antineoplastic activity; cancer cell culture; enzyme activation; cell line, tumor; bladder cancer; cancer model; urinary bladder neoplasms; cancer inhibition; gene expression regulation, neoplastic; murinae; neoplasm invasiveness; bladder carcinoma; choline kinase; therapeutic target; tumor promoter; choline kinase alpha; mn 58 b; phosphotransferase inhibitor; bladder carcinogenesis |
| Journal Title: | Oncogene |
| Volume: | 28 |
| Issue: | 26 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-07-02 |
| Start Page: | 2425 |
| End Page: | 2435 |
| Language: | English |
| DOI: | 10.1038/onc.2009.91 |
| PUBMED: | 19448670 |
| PROVIDER: | scopus |
| PMCID: | PMC2908237 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: ONCNE" - "Source: Scopus" |
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