A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 19155308.
- Also identified by DOI 10.1158/0008-5472.CAN-08-2473 and PMC identifier 2636510.
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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.
Medical subject headings
- Cell Transformation, Neoplastic
- Cyclin-Dependent Kinase 6
- T-Lymphocytes
- Thymus Gland
- Thymus Neoplasms