Activated PI3K signaling as an endogenous inducer of p53 in human cancer.
Complex pathways exist in mammalian cells to regulate the expression and activity of oncogenes and tumor suppressor genes. Defining these regulatory pathways is an important step towards being able to interfere with tumorigenesis. Here we discuss our recent study indicating that activation of the phosphoinositide 3-kinase (PI3K) signaling pathway through inactivating mutations in PTEN or activating mutations in PIK3CA causes functional activation of p53 signaling in human cells.(1)ur data suggest that activation of p53 is a fail-safe mechanism triggered by loss of PTEN or oncogenic activation of PI3K, and furthermore, that these events provide selective pressure to mutate p53.
Lee
Carolyn
C
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.
Kim
Jung-Sik
JS
Waldman
Todd
T
D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human