| First Author | Utermark T | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 14 | Pages | 1573-86 |
| PubMed ID | 22802530 | Mgi Jnum | J:185640 |
| Mgi Id | MGI:5429612 | Doi | 10.1101/gad.191973.112 |
| Citation | Utermark T, et al. (2012) The p110alpha and p110beta isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 26(14):1573-86 |
| abstractText | 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 p110alpha blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer. Surprisingly, p110beta ablation results in both increased ductal branching and tumorigenesis. Biochemical analyses suggest a competition model in which the less active p110beta competes with the more active p110alpha for receptor binding sites, thereby modulating the level of PI3K activity associated with activated receptors. Our findings demonstrate a novel p110beta-based regulatory role in receptor-mediated PI3K activity and identify p110alpha as an important target for treatment of HER2-positive disease. |
