Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers

  • Nat Genet. 2000 Nov;26(3):291-9. doi: 10.1038/81583.
J J Jacobs  1 ,  P Keblusek ,  E Robanus-Maandag ,  P Kristel ,  M Lingbeek ,  P M Nederlof ,  T van Welsem ,  M J van de Vijver ,  E Y Koh ,  G Q Daley ,  M van Lohuizen
Affiliations
  • 1. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
PMID: 11062467 DOI: 10.1038/81583
Abstract

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.