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

共 50 条

[21] Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors
Gomatou, Georgia
Trontzas, Ioannis
Ioannou, Stephanie
Drizou, Maria
Syrigos, Nikolaos
Kotteas, Elias
MOLECULAR BIOLOGY REPORTS, 2021, 48 (01) : 915 - 925
[22] Cyclin-dependent kinase 6 is regulated by microRNA 124 in medulloblastoma
Pierson, Jessica
Fan, Rong
Vibhakar, Rajeev
NEURO-ONCOLOGY, 2008, 10 (03) : 377 - 377
[23] Cyclin-dependent kinase 4/6 inhibition in cancer therapy
Johnson, Neil
Shapiro, Geoffrey I.
CELL CYCLE, 2012, 11 (21) : 3913 - 3913
[24] Increased cyclin-dependent kinase 6 expression in bladder cancer
Wang, Gang
Zheng, Lingyan
Yu, Zhijian
Liao, Guodong
Lu, Liqin
Xu, Rujun
Zhao, Zhongsheng
Chen, Guangdi
ONCOLOGY LETTERS, 2012, 4 (01) : 43 - 46
[25] The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal Development
Saito, Masanori
Mulati, Mieradili
Talib, S. Zakiah A.
Kaldis, Philipp
Takeda, Shu
Okawa, Atsushi
Inose, Hiroyuki
SCIENTIFIC REPORTS, 2016, 6
[26] Re: Preclinical and clinical development of cyclin-dependent kinase modulators
Darzynkiewicz, Z
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (14) : 1184 - 1185
[27] Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol
Shapiro, GI
CLINICAL CANCER RESEARCH, 2004, 10 (12) : 4270S - 4275S
[28] The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal Development
Masanori Saito
Mieradili Mulati
S. Zakiah A. Talib
Philipp Kaldis
Shu Takeda
Atsushi Okawa
Hiroyuki Inose
Scientific Reports, 6
[29] The role of cyclin-dependent kinase 5 in brain development and degeneration
Tsai, LH
CELLULAR & MOLECULAR BIOLOGY LETTERS, 2003, 8 (2A) : 546 - 547
[30] Cyclin-dependent kinase 5 is required for normal cerebellar development
Kumazawa, A.
Mita, N.
Hirasawa, M.
Adachi, T.
Suzuki, H.
Shafeghat, N.
Kulkarni, A. B.
Mikoshiba, K.
Inoue, T.
Ohshima, T.
MOLECULAR AND CELLULAR NEUROSCIENCE, 2013, 52 : 97 - 105

← 1 2 3 4 5 →