The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation.
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.
Zhao
Jean J
JJ
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. jean_zhao@dfci.harvard.edu
Cheng
Hailing
H
Jia
Shidong
S
Wang
Li
L
Gjoerup
Ole V
OV
Mikami
Aki
A
Roberts
Thomas M
TM
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D058534:Class I Phosphatidylinositol 3-Kinases; D017353:Gene Deletion; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D007527:Isoenzymes; D015513:Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases