Activation of the PIK3CA/AKT Pathway Suppresses Senescence Induced by an Activated RAS Oncogene to Promote Tumorigenesis

Journal article

Mutations in both RAS and the PTEN/PIK3CA/AKT signaling module are found in the same human tumors. PIK3CA and AKT are downstream effectors of RAS, and the selective advantage conferred by mutation of two genes in the same pathway is unclear. Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS. Moreover, concurrent activation of RAS and PIK3CA/AKT impairs RAS-induced senescence. In vivo, bypass of RAS-induced sene...

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Authors: Kennedy, A; Morton, J; Manoharan, I; Nelson, D; Jamieson, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier Publisher's website
• Journal: Molecular Cell Journal website
• Volume: 42
• Issue: 1
• Pages: 36-49
• Publication date: 2011-04-08
• Acceptance date: 2011-01-27
• DOI: 10.1016/j.molcel.2011.02.020
• EISSN: 1097-4164
• ISSN: 1097-2765
• Pmid: 21474066
• Language: English
• Keywords: Mice, Transgenic; Cell Aging; Research Support, N.I.H., Extramural; Enzyme Activation; Research Support, Non-U.S. Gov't; Cell Proliferation; Cell Line, Transformed; research-article; Pancreatic Neoplasms; Disease Models, Animal; Aged; Mutation; Humans; Proto-Oncogene Proteins c-akt; Female; Male; Signal Transduction; Phosphatidylinositol 3-Kinases; Mice, Knockout; Animals; Journal Article; Gene Expression Regulation, Neoplastic; Mice; SBTMR; Genes, ras; PTEN Phosphohydrolase; Middle Aged; Neoplasms