Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo |
| |
Authors: | Xu Mai Yu Qing Subrahmanyam Ramesh Difilippantonio Michael J Ried Thomas Sen Jyoti Misra |
| |
Affiliation: | Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, 5600 Nathan Shock Drive, Room 4B08 GRC, Baltimore, MD 21224, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|