Nature Genetics
26, 291 - 299 (2000)
doi:10.1038/81583
Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancersJacqueline J.L. Jacobs1, Petra Keblusek1, Els Robanus-Maandag2, 3, Petra Kristel2, 3, Merel Lingbeek1, Petra M. Nederlof2, Tibor van Welsem2, Marc J. van de Vijver2, 3, Eugene Y. Koh4, George Q. Daley4
& Maarten van Lohuizen11
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 2
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4
Whitehead Institute, Cambridge, Massachusetts, USA.
Correspondence should be addressed to Maarten van Lohuizen lohuizen@nki.nlTo 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 (p19ARF). TBX2 represses the Cdkn2a (p19ARF) promoter and attenuates E2F1, Myc or HRAS-mediated induction of Cdkn2a (p19ARF). 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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