Proceedings of the National Academy of Sciences · 2006 · 223 citations · 26 references
Life SciencesMolecular BiologyOncologyCell SignalingMolecular OncologySignal TransductionCancer Cell SignalingCancer ProgressionGrowth Factor SignalingLipid SignalingOncogenic ProliferationOncogenic Signaling PathwaysGrowth FactorsOncogenic TransformationPhosphatidylinositol 3-Kinase PathwayPhosphatidylinositol 3-Kinase-akt SignalingPhosphoinositide 3-Kinase PathwayPhosphoinositide 3-Kinase SignalingPi3k SignalingPik3ca Mutations
Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110alpha, we generated mice carrying a conditionally targeted allele of the PIK3CA gene. Here, we report that PIK3CA-knockout mouse embryonic fibroblasts are deficient in cellular signaling in response to various growth factors, unable to differentiate into adipocytes, and resistant to oncogenic transformation induced by a variety of oncogenic receptor tyrosine kinases, indicating a fundamental role for p110alpha in these biological processes.
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