Msh2-dependent DNA repair mitigates a unique susceptibility of B cell progenitors to c-Myc-induced lymphomas
AUTOR(ES)
Nepal, Rajeev M.
FONTE
National Academy of Sciences
RESUMO
C-Myc is one of the most common targets of genetic alterations in human cancers. Although overexpression of c-Myc in the B cell compartment predisposes to lymphomas, secondary mutations are required for disease manifestation. In this article, we show that genetic deficiencies causing arrested B cell development and accumulation of B cell progenitors lead to accelerated lymphomagenesis in Eμ c-myc transgenic mice. This result suggests that B cell progenitors are more prone than their mature counterparts to developing secondary oncogenic lesions that complement c-Myc in promoting transformation. To investigate the nature of these oncogenic lesions, we examined Eμ c-myc mice deficient in mismatch repair function. We report that Msh2−/− Eμ c-myc and Msh2G674A/G674A Eμ c-myc mice rapidly succumb to pro-B cell stage lymphomas, indicating that Msh2-dependent mismatch repair function actively suppresses c-Myc-associated oncogenesis during early B cell development.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2773990Documentos Relacionados
- Ornithine decarboxylase is a mediator of c-Myc-induced apoptosis.
- c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release
- c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines.
- c-Myc-induced Aberrant DNA Synthesis and Activation of DNA Damage Response in p300 Knockdown Cells*
- Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF