Proceedings of the National Academy of Sciences · 2006 · 418 citations · 28 references
MedicineCancer BiologyOncologyMolecular OncologyOncogenesSignal TransductionCancer Cell SignalingCancer ProgressionMalignant NeoplasmsOncogene ActivationOncogene MutationsOncogenic Signaling PathwaysCancer Signaling PathwaysPhosphatidylinositol 3-Kinase PathwayPhosphatidylinositol 3-Kinase-akt PathwayPhosphoinositide 3-Kinase SignalingPi3 Kinase-akt SignalingPi3k SignalingPi3k-akt Signaling PathwayPik3ca Mutations
The PIK3CA gene, coding for the catalytic subunit p110alpha of class IA phosphatidylinositol 3-kinases (PI3Ks), is frequently mutated in human cancer. Mutated p110alpha proteins show a gain of enzymatic function in vitro and are oncogenic in cell culture. Here, we show that three prevalent mutants of p110alpha, E542K, E545K, and H1047R, are oncogenic in vivo. They induce tumors in the chorioallantoic membrane of the chicken embryo and cause hemangiosarcomas in the animal. These tumors are marked by increased angiogenesis and an activation of the Akt pathway. The target of rapamycin inhibitor RAD001 blocks tumor growth induced by the H1047R p110alpha mutant. The in vivo oncogenicity of PIK3CA mutants in an avian species strongly suggests a critical role for these mutated proteins in human malignancies.
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High Frequency of Mutations of the <i>PIK3CA</i> Gene in Human Cancers
Yardena Samuels, Zhenghe Wang, Alberto Bardelli et al. · Science · 2004 · 3.4K citations
Brian Druker, Charles L. Sawyers, Hagop M. Kantarjian et al. · New England Journal of Medicine · 2001 · 2.7K citations · Full text
Medicine, Hematology, Oncology +17