| Literature DB >> 19155308 |
Miaofen G Hu1, Amit Deshpande, Miriam Enos, Daqin Mao, Elisabeth A Hinds, Guo-fu Hu, Rui Chang, Zhuyan Guo, Marei Dose, Changchuin Mao, Philip N Tsichlis, Fotini Gounari, Philip W Hinds.
Abstract
Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies.Entities:
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Year: 2009 PMID： 19155308 PMCID： PMC2636510 DOI： 10.1158/0008-5472.CAN-08-2473
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701