INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
AUTOR(ES)
Schmitt, Clemens A.
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products. To compare the impact of these loci on tumor development and treatment response, the Eμ–myc transgenic lymphoma model was used to generate genetically defined tumors with mutations in the INK4a/ARF, Rb, or p53 genes. Like p53 null lymphomas, INK4a/ARF null lymphomas formed rapidly, were highly invasive, displayed apoptotic defects, and were markedly resistant to chemotherapy in vitro and in vivo. Furthermore, INK4a/ARF−/− lymphomas displayed reduced p53 activity despite the presence of wild-type p53 genes. Consequently, INK4a/ARF and p53 mutations lead to aggressive tumors by disrupting overlapping tumor suppressor functions. These data have important implications for understanding the clinical behavior of human tumors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=317110Documentos Relacionados
- Ink4a/Arf expression is a biomarker of aging
- Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function
- Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
- Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging
- Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice
