A Requirement for CDK6 in Thymocyte Development and Tumorigenesis

CDK6 promotes cell cycle progression and is over-expressed 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 concomita...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-01, Vol.69 (3), p.810-818
Main Authors: Hu, Miaofen G, Deshpande, Amit, Enos, Miriam, Mao, Daqin, Hinds, Elisabeth A, Hu, Guo-fu, Chang, Rui, Guo, Zhuyan, Dose, Marei, Mao, Changchuin, Tsichlis, Philip N, Gounari, Fotini, Hinds, Philip W
Format: Article
Language:English
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Summary:CDK6 promotes cell cycle progression and is over-expressed 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 (DN) 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 demonstrate 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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-2473