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...

Full description

Saved in:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page 818
container_issue 3
container_start_page 810
container_title Cancer research (Chicago, Ill.)
container_volume 69
creator 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
description 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.
doi_str_mv 10.1158/0008-5472.CAN-08-2473
format article
fullrecord <record><control><sourceid>pubmedcentral</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2636510</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_2636510</sourcerecordid><originalsourceid>FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_26365103</originalsourceid><addsrcrecordid>eNqlTt1qwjAY_RBFq_MRBnmBuqRp2u5mUKoyGOxCeh8y_dRIk3SJFfr2K2MMvPbqnMP54QA8M7piTBQvlNIiFmmerKryMx54kuZ8BBETvIjzNBVjiP4zM5iHcBmkYFRMYcZemRCcFhGUJdnhd6c9GrRXcnSeVOuPjGhL6nNv3L6_IlnjDRvX_iaUPZC6M87rE1oMOjzB5KiagMs_XMDbdlNX73HbfRk87IeSV41svTbK99IpLe8dq8_y5G4yyXg2_OMPD_wAA4FZFg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A Requirement for CDK6 in Thymocyte Development and Tumorigenesis</title><source>EZB-FREE-00999 freely available EZB journals</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-08-2473</identifier><identifier>PMID: 19155308</identifier><language>eng</language><ispartof>Cancer research (Chicago, Ill.), 2009-01, Vol.69 (3), p.810-818</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27898,27899</link.rule.ids></links><search><creatorcontrib>Hu, Miaofen G</creatorcontrib><creatorcontrib>Deshpande, Amit</creatorcontrib><creatorcontrib>Enos, Miriam</creatorcontrib><creatorcontrib>Mao, Daqin</creatorcontrib><creatorcontrib>Hinds, Elisabeth A</creatorcontrib><creatorcontrib>Hu, Guo-fu</creatorcontrib><creatorcontrib>Chang, Rui</creatorcontrib><creatorcontrib>Guo, Zhuyan</creatorcontrib><creatorcontrib>Dose, Marei</creatorcontrib><creatorcontrib>Mao, Changchuin</creatorcontrib><creatorcontrib>Tsichlis, Philip N</creatorcontrib><creatorcontrib>Gounari, Fotini</creatorcontrib><creatorcontrib>Hinds, Philip W</creatorcontrib><title>A Requirement for CDK6 in Thymocyte Development and Tumorigenesis</title><title>Cancer research (Chicago, Ill.)</title><description>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.</description><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNqlTt1qwjAY_RBFq_MRBnmBuqRp2u5mUKoyGOxCeh8y_dRIk3SJFfr2K2MMvPbqnMP54QA8M7piTBQvlNIiFmmerKryMx54kuZ8BBETvIjzNBVjiP4zM5iHcBmkYFRMYcZemRCcFhGUJdnhd6c9GrRXcnSeVOuPjGhL6nNv3L6_IlnjDRvX_iaUPZC6M87rE1oMOjzB5KiagMs_XMDbdlNX73HbfRk87IeSV41svTbK99IpLe8dq8_y5G4yyXg2_OMPD_wAA4FZFg</recordid><startdate>20090120</startdate><enddate>20090120</enddate><creator>Hu, Miaofen G</creator><creator>Deshpande, Amit</creator><creator>Enos, Miriam</creator><creator>Mao, Daqin</creator><creator>Hinds, Elisabeth A</creator><creator>Hu, Guo-fu</creator><creator>Chang, Rui</creator><creator>Guo, Zhuyan</creator><creator>Dose, Marei</creator><creator>Mao, Changchuin</creator><creator>Tsichlis, Philip N</creator><creator>Gounari, Fotini</creator><creator>Hinds, Philip W</creator><scope>5PM</scope></search><sort><creationdate>20090120</creationdate><title>A Requirement for CDK6 in Thymocyte Development and Tumorigenesis</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_26365103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Miaofen G</creatorcontrib><creatorcontrib>Deshpande, Amit</creatorcontrib><creatorcontrib>Enos, Miriam</creatorcontrib><creatorcontrib>Mao, Daqin</creatorcontrib><creatorcontrib>Hinds, Elisabeth A</creatorcontrib><creatorcontrib>Hu, Guo-fu</creatorcontrib><creatorcontrib>Chang, Rui</creatorcontrib><creatorcontrib>Guo, Zhuyan</creatorcontrib><creatorcontrib>Dose, Marei</creatorcontrib><creatorcontrib>Mao, Changchuin</creatorcontrib><creatorcontrib>Tsichlis, Philip N</creatorcontrib><creatorcontrib>Gounari, Fotini</creatorcontrib><creatorcontrib>Hinds, Philip W</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Miaofen G</au><au>Deshpande, Amit</au><au>Enos, Miriam</au><au>Mao, Daqin</au><au>Hinds, Elisabeth A</au><au>Hu, Guo-fu</au><au>Chang, Rui</au><au>Guo, Zhuyan</au><au>Dose, Marei</au><au>Mao, Changchuin</au><au>Tsichlis, Philip N</au><au>Gounari, Fotini</au><au>Hinds, Philip W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Requirement for CDK6 in Thymocyte Development and Tumorigenesis</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><date>2009-01-20</date><risdate>2009</risdate><volume>69</volume><issue>3</issue><spage>810</spage><epage>818</epage><pages>810-818</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><abstract>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.</abstract><pmid>19155308</pmid><doi>10.1158/0008-5472.CAN-08-2473</doi></addata></record>
fulltext fulltext
identifier ISSN: 0008-5472
ispartof Cancer research (Chicago, Ill.), 2009-01, Vol.69 (3), p.810-818
issn 0008-5472
1538-7445
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2636510
source EZB-FREE-00999 freely available EZB journals
title A Requirement for CDK6 in Thymocyte Development and Tumorigenesis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-03-05T18%3A44%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmedcentral&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Requirement%20for%20CDK6%20in%20Thymocyte%20Development%20and%20Tumorigenesis&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=Hu,%20Miaofen%20G&rft.date=2009-01-20&rft.volume=69&rft.issue=3&rft.spage=810&rft.epage=818&rft.pages=810-818&rft.issn=0008-5472&rft.eissn=1538-7445&rft_id=info:doi/10.1158/0008-5472.CAN-08-2473&rft_dat=%3Cpubmedcentral%3Epubmedcentral_primary_oai_pubmedcentral_nih_gov_2636510%3C/pubmedcentral%3E%3Cgrp_id%3Ecdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_26365103%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/19155308&rfr_iscdi=true