p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas
AUTOR(ES)
Singh, Bhuvanesh
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Interactions between the p53 and PI3K/AKT pathways play a significant role in the determination of cell death/survival. In benign cells these pathways are interrelated through the transcriptional regulation of PTEN by p53, which is required for p53-mediated apoptosis. PTEN exerts its effects by decreasing the phosphorylated AKT fraction, thereby diminishing prosurvival activities. However, the link between these pathways in cancer is not known. In this study, PIK3CA, encoding the p110α catalytic subunit of PI3K, is identified as an oncogene involved in upper aerodigestive tract (UADT) carcinomas. Simultaneous abnormalities in both pathways are rare in primary tumors, suggesting that amplification of PIK3CA and mutation of p53 are mutually exclusive events and either event is able to promote a malignant phenotype. Moreover, the negative effect of p53 induction on cell survival involves the transcriptional inhibition of PIK3CA that is independent of PTEN activity, as PTEN is not expressed in the primary tumors. Conversely, constitutive activation of PIK3CA results in resistance to p53-related apoptosis in PTEN deficient cells. Thus, p53 regulates cell survival by inhibiting the PI3K/AKT prosurvival signal independent of PTEN in epithelial tumors. This inhibition is required for p53-mediated apoptosis in malignant cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=152354Documentos Relacionados
- p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.
- Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas
- p53 gene mutations, and CYP1A1 and GSTM1 genotypes in pulmonary squamous cell carcinomas.
- p53 Overexpression in laryngeal squamous cell carcinoma and dysplasia
- PIK3CA exon 20 mutations are associated with poor prognosis in breast cancer patients