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

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.