Myc-Mediated Proliferation and Lymphomagenesis, but Not Apoptosis, Are Compromised by E2f1 Loss

• Autores: Jennifer Brennan, Troy A. Baudino, Kirsteen H. Maclean
• Localización: Molecular cell, ISSN 1097-2765, Vol. 12, Nº 4, 2003, pág. 905
• Idioma: inglés
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• Resumen

  • Myc and E2f1 promote cell cycle progression, but overexpression of either can trigger p53-dependent apoptosis. Mice expressing an Eμ-Myc transgene in B lymphocytes develop lymphomas, the majority of which sustain mutations of either the Arf or p53 tumor suppressors. Eμ-Myc transgenic mice lacking one or both E2f1 alleles exhibited a slower onset of lymphoma development associated with increased expression of the cyclin-dependent kinase inhibitor p27Kip1 and a reduced S phase fraction in precancerous B cells. In contrast, Myc-induced apoptosis and the frequency of Arf and p53 mutations in lymphomas were unaffected by E2f1 loss. Therefore, Myc does not require E2f1 to induce Arf, p53, or apoptosis in B cells, but depends upon E2f1 to accelerate cell cycle progression and downregulate p27Kip1.