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-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKalpha show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKalpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKalpha 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 ChoKalpha potentiate both tumor formation (P< or =0.0001) and aggressiveness of the disease on different end points (P=0.011). Accordingly, increased levels of ChoKalpha significantly reduce survival of mice with bladder cancer (P=0.05). Finally, treatment with a ChoKalpha-specific inhibitor resulted in a significant inhibition of tumor growth (P=0.02) and in a relevant increase in survival (P=0.03).
journal_name
Oncogenejournal_title
Oncogeneauthors
Hernando E,Sarmentero-Estrada J,Koppie T,Belda-Iniesta C,Ramírez de Molina V,Cejas P,Ozu C,Le C,Sánchez JJ,González-Barón M,Koutcher J,Cordón-Cardó C,Bochner BH,Lacal JC,Ramírez de Molina Adoi
10.1038/onc.2009.91subject
Has Abstractpub_date
2009-07-02 00:00:00pages
2425-35issue
26eissn
0950-9232issn
1476-5594pii
onc200991journal_volume
28pub_type
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