Our findings indicate that PIK3CA mutations are a common event that can occur early in bladder carcinogenesis and support the notion that papillary and muscle-invasive tumors arise through different molecular pathways.
Inactivation of the tumor suppressor gene PTEN leads to a constitutively active PI3K pathway, which plays a role in the early steps of endometrial tumorigenesis.
They integrate known tumorigenesis (Wnt, PI3K, MAP kinase, hypoxia, G protein-coupled receptor), neurologic, insulin-signaling, and NFAT-immune pathways into an intricate biological network.
Our data suggest that PIK3CA mutations contribute to the invasion step from intramucosal carcinoma to invasive carcinoma in colorectal carcinogenesis in FAP and HNPCC patients at a similar extent to that seen in sporadic patients.
(2007) use mouse models of Ras-mediated tumorigenesis to show that the interaction of Ras with a single isoform of phosphatidylinositol 3-kinase (PI3K), called p110alpha (PIK3CA), is critical for tumor formation.
The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate.
In addition to the induction of HIF by hypoxia, its expression is induced by the loss of tumor suppressors VHL, PTEN, TSC1/2, PML, and SDH, as well as by the increased activity of PI3K and/or MAPK signaling pathways, underscoring the significance of HIF in oncogenesis.
Activated phosphoinositide 3-kinase (PI3K) and its downstream target Akt/PKB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis.
Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis.
The epidermal growth factor receptor- (EGFR) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is associated with tumorigenesis and progression.
Most strikingly, in an animal model of prostate tumour formation induced by Pten loss, ablation of p110beta (also known as Pik3cb), but not that of p110alpha (also known as Pik3ca), impeded tumorigenesis with a concomitant diminution of Akt phosphorylation.
The data further support that oncogenic PIK3CA may play a critical role in pharyngeal carcinogenesis, and the mutant-enriched sequencing methods for PIK3CA are sensitive and reliable ways to detect PIK3CA mutations in clinical samples.
The phosphoinositide-3 kinase (PI3K)/Akt signal pathway plays a key role in the tumorigenesis of many cancers and in the subsequent development of drug resistance.
These results suggest that PIK3CA mutations in HNSCC are likely to be oncogenic and may significantly contribute to HNSCC carcinogenesis and pave attractive target for therapeutic prevention.