4.8 Article

The p110α isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.0607899103

关键词

adipocyte differentiation; cancer therapy; conditional knockout; PIK3CA

资金

  1. NCI NIH HHS [R37 CA030002, 5P50 CA 090381-05, R01 CA030002, P01 CA089021, P01 CA050661, P01 CA 089021, P50 CA090381, P01 CA 50661, CA 30002] Funding Source: Medline

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Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110 alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110 alpha, 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 p110 alpha in these biological processes.

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