The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.

Abstract:

:Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer. Surprisingly, p110β ablation results in both increased ductal branching and tumorigenesis. Biochemical analyses suggest a competition model in which the less active p110β competes with the more active p110α for receptor binding sites, thereby modulating the level of PI3K activity associated with activated receptors. Our findings demonstrate a novel p110β-based regulatory role in receptor-mediated PI3K activity and identify p110α as an important target for treatment of HER2-positive disease.

journal_name

Genes Dev

journal_title

Genes & development

authors

Utermark T,Rao T,Cheng H,Wang Q,Lee SH,Wang ZC,Iglehart JD,Roberts TM,Muller WJ,Zhao JJ

doi

10.1101/gad.191973.112

subject

Has Abstract

pub_date

2012-07-15 00:00:00

pages

1573-86

issue

14

eissn

0890-9369

issn

1549-5477

pii

26/14/1573

journal_volume

26

pub_type

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