Mutation of the PIK3CA oncogene in human cancers

Abstract

It is now well established that cancer is a genetic disease and that somatic mutations of oncogenes and tumour suppressor genes are the initiators of the carcinogenic process. The phosphatidylinositol 3-kinase signalling pathway has previously been implicated in tumorigenesis, and evidence over the past year suggests a pivotal role for the phosphatidylinositol 3-kinase catalytic subunit, PIK3CA, in human cancers. In this review, we analyse recent reports describing PIK3CA mutations in a variety of human malignancies, and discuss their possible implications for diagnosis and therapy.

Repression of cancer cell senescence by PKCι

“…Both overexpression and activation could be induced by mutant, constitutively active PIK3CA. PIK3CA mutations are present in 25-30% of breast cancers (Karakas et al, 2006). As we and others have observed overexpression of PKCi in 70-80% of breast cancers, additional factors are probably also able to drive this overexpression.…”

“…Mutational activation of PI-3-kinase most frequently occurs as a result of point mutations in the PIK3CA gene, which are found in 25-30% of breast cancers and at a lower frequency in other cancer types (Karakas et al, 2006). Amplification of the PIK3CB gene has also been reported, although this appears to be a relatively rare event (Crowder et al, 2009).…”

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

“…155 The Akt/mTOR pathway may be activated through cell surface receptors like the insulin-like growth factor 1 receptor and HER-2, but in addition through pathological activation of the PI3K/Akt system. Thus, activating mutations in exons 9 or 20 in the PI3K subunit PIK3CA have been detected in 15-25% of all breast cancers, 156 but are seen more frequently among oestrogen receptor-positive tumours belonging to the luminal A class. 157 In addition, approximately 5% of breast cancers may harbour activating mutations in AKT.…”

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

“…1,2 Here, PI3K has improved access to its plasma membrane-located substrates and in particular converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ). The latter in turn serves as a binding site for pleckstrin homology domain containing proteins, especially the serine-threonine kinase Akt/PKB and the phosphoinosite-dependent protein kinase-1 (PDK1).…”