A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis

被引：99

作者：

Hu, Miaofen G. ^{[1
]}

Deshpande, Amit ^{[4
]}

Enos, Miriam ^{[1
]}

Mao, Daqin ^{[1
]}

Hinds, Elisabeth A. ^{[1
]}

Hu, Guo-fu ^{[2
]}

Chang, Rui ^{[1
,3
]}

Guo, Zhuyan ^{[1
,5
]}

Dose, Marei ^{[1
,6
]}

Mao, Changchuin ^{[1
]}

Tsichlis, Philip N. ^{[1
]}

Gounari, Fotini ^{[1
,6
]}

Hinds, Philip W. ^{[1
]}

机构：

[1] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA

[4] Univ Calif Los Angeles, Dent Res Inst, Los Angeles, CA 90024 USA

[5] MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA

[6] Univ Chicago, Dept Med, Comm Immunol, Chicago, IL 60637 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 03期

关键词：

T-CELL DEVELOPMENT; SIGNALING PATHWAY; GENE-EXPRESSION; NOTCH; INDUCTION; INSULIN; LINEAGE; CDK6; FATE; SUPPRESSION;

D O I：

10.1158/0008-5472.CAN-08-2473

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 lympho-magenesis 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. [Cancer Res 2009; 69(3):810-8]

引用

页码：810 / 818

页数：9

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