Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers

被引:312
作者
Jacobs, JJL
Keblusek, P
Robanus-Maandag, E
Kristel, P
Lingbeek, M
Nederlof, PM
van Welsem, T
van de Vijver, MJ
Koh, EY
Daley, GQ
van Lohuizen, M [1 ]
机构
[1] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands
[2] Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands
[3] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands
[4] Whitehead Inst, Cambridge, MA 02142 USA
关键词
D O I
10.1038/81583
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
To identify new immortalizing genes with potential roles in tumorigenesis, we performed a genetic screen aimed to bypass the rapid and tight senescence arrest of primary fibroblasts deficient for the oncogene Bmi1. We identified the T-box member TBX2 as a potent immortalizing gene that acts by downregulating Cdkn2a (p19(ARF)). TBX2 represses the Cdkn2a (p19(ARF)) promoter and attenuates E2F1, Myc or HRAS-mediated induction of Cdkn2a (p19(ARF)). We found TBX2 to be amplified in a subset of primary human breast cancers, indicating that it might contribute to breast cancer development.
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页码:291 / 299
页数:9
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