%0 Journal Article
%T Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it play?
%A Michael John Fry
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr312
%X Phosphoinositide 3-kinase (PI3K) was first detected in the 1980s as a novel lipid kinase activity found associated with several oncogene products (v-Ros, v-Src and polyoma virus middle T antigen [mT]) and subsequently with many activated growth factor receptor complexes [1]. It is surprising, given this beginning, that it was not until the late 1990s that a PI3K was isolated, first as a retroviral oncogene and then implicated in several human cancers [2]. It is now clear that alterations in PI3K signalling cassettes can lead to changes in a number of cell functions that contribute to the transformed phenotype, including cell growth and proliferation, differentiation, cell survival, adhesion and cell motility [2,3]. The PI3K family of enzymes, their targets, and regulators are thus now considered important potential therapeutic targets [4]. In this review, the PI3K superfamily will be briefly described with respect to how these enzymes function and are regulated. The emerging data implicating PI3K signalling in human cancer, with special reference to possible roles in breast disease, will be considered.The PI3K superfamily is defined by sequence motifs present in the catalytic domain of these enzymes [1,5]. There are at least 12 members of this family present in the human genome that can be divided into two main groups. The true PI3Ks display lipid kinase and some protein kinase activity, and are further subdivided into Class I-III enzymes. The PI3K-related enzymes (Class IV) are large proteins that possess protein kinase activity only [6].Class I PI3Ks have been studied most extensively and are best understood. It was a Class I PI3K that was originally found associated with oncogene products, and a member of this family was the first to be cloned [1]. Class I PI3Ks are activated by diverse cell surface receptors including G-protein-coupled receptors, by receptors with either intrinsic or associated protein-tyrosine kinase (PTK) activity, by association with tyrosine
%K Akt
%K ataxia telangiectasia mutated
%K BRCA1
%K phosphoinositide 3-kinase
%K PTEN
%U http://breast-cancer-research.com/content/3/5/304