Physiological expression of the PI3K activating mutation Pik3caH1047R combines with Apc loss to promote development of invasive intestinal adenocarcinomas in mice
- Hare, LM; Phesse, TJ; Waring, PM; Montgomery, KG; Kinross, KM; Mills, K; Roh, V; Heath, JK; Ramsay, RG; Ernst, M; Phillips, WA;
Publication Year 2013-12-09, Volume 458, Issue #2, Page 251-8
- Journal Title
- Biochemical Journal
- Publication Type
- Journal Article
- PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), is mutated in around 20% of sporadic colorectal cancers (CRCs) but the role of these mutations in the pathogenesis of CRC remains unclear. We used a novel mouse model to investigate the role of Pik3caH1047R mutation, the most common PIK3CA mutation in CRC, during the development and progression of intestinal cancer. Our results demonstrate that Pik3caH1047R, when expressed at physiological levels, is insufficient to initiate intestinal tumourigenesis. However,in the context of Apc loss, which is observed in 80% of CRCs and by itself results in benign intestinal adenomas, Pik3caH1047R mutation promotes the development of highly aggressive and invasive adenocarcinomas in both the small and large intestines. Our findings show that an activating Pik3ca mutation can cooperate with Apc loss to drive the progression of gastrointestinal cancer and thus this diseasemay be susceptible to therapeutic targeting using PI3K pathway inhibitors.
- PORTLAND PRESS LTD
- adenomatous polyposis coli (Apc), colorectal cancer, mouse model, phosphoinositide 3-kinase (PI3K), phosphoinositide 3-kinase, catalytic, α polypeptide (Pik3ca).
- WEHI Research Division(s)
- Cell Signalling And Cell Death
- Publisher's Version
- Rights Notice
- © 2013 The Authors Journal compilation © 2013 Biochemical Society
Creation Date: 2014-01-14 03:36:38Last Modified: 0001-01-01 12:00:00