β-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo

Mai Xu, Qing Yu, Ramesh Subrahmanyam, Michael J. Difilippantonio, Thomas Ried, Jyoti Misra Sen

Research output: Contribution to journalArticle

Abstract

The expression of β-catenin, a potent oncogene, is causally linked to tumorigenesis. Therefore, it was surprising that the transgenic expression of oncogenic β-catenin in thymocytes resulted in thymic involution instead of lymphomagenesis. In this report, we demonstrate that this is because the expression of oncogenic β-catenin induces DNA damage, growth arrest, oncogene-induced senescence (OIS), and apoptosis of immature thymocytes. In p53-deficient mice, the expression of oncogenic β-catenin still results in DNA damage and OIS, but the thymocytes survive and eventually progress to thymic lymphoma. β-Catenin-induced thymic lymphomas are distinct from lymphomas that arise in p53-/- mice. They are CD4- CD8-, while p53-dependent lymphomas are largely CD4+ CD8+, and they develop at an earlier age and in the absence of c-Myc expression or Notch1 signaling. Thus, we report that oncogenic β-catenin-induced, p53-independent growth arrest and OIS and p53-dependent apoptosis protect developing thymocytes from transformation by oncogenic β-catenin.

Original languageEnglish (US)
Pages (from-to)1713-1723
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number5
DOIs
StatePublished - Mar 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

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