p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas Journal Article
| Authors: | Singh, B.; Reddy, P. G.; Goberdhan, A.; Walsh, C.; Dao, S.; Ngai, I.; Chou, T. C.; O-Charoenrat, P.; Levine, A. J.; Rao, P. H.; Stoffel, A. |
| Article Title: | p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas |
| Abstract: | 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. |
| Keywords: | signal transduction; protein kinase b; gene mutation; human cell; proto-oncogene proteins; squamous cell carcinoma; carcinoma, squamous cell; cell survival; apoptosis; gene amplification; lung neoplasms; down-regulation; lung cancer; tumor cells, cultured; phosphatidylinositol 3 kinase; protein p53; oncogene; gene expression regulation, neoplastic; regulatory mechanism; transcription regulation; head and neck cancer; head and neck neoplasms; protein-serine-threonine kinases; tumor suppressor proteins; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; pten phosphohydrolase; tumor suppressor protein p53; dna mutational analysis; protein subunits; catalytic domain; phosphoric monoester hydrolases; squamous cell carcinomas; pi3k; p53; humans; human; priority journal; article |
| Journal Title: | Genes and Development |
| Volume: | 16 |
| Issue: | 8 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2002-04-15 |
| Start Page: | 984 |
| End Page: | 993 |
| Language: | English |
| DOI: | 10.1101/gad.973602 |
| PUBMED: | 11959846 |
| PROVIDER: | scopus |
| PMCID: | PMC152354 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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