Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase

摘要: Mice with heterozygous deletion of the PTEN tumor suppressor gene develop a range epithelial neoplasia as well lymphoid hyperplasia. Previous studies suggest that suppresses formation by acting phosphoinositide phosphatase to limit signaling 3-kinase (PI3K). Here, we examined effect deleting various regulatory subunits PI3K (p85α and p85β) on hyperplasia in PTEN+/- mice. Interestingly, found loss one p85α allele or without p85β led increased incidence intestinal polyps. Signaling downstream was enhanced PTEN+/-p85α+/-p85β-/- polyps, judged an fraction both cells cytoplasmic staining transcription factor FKHR positive for proliferation marker Ki-67. In contrast, prostate intraepithelial not significantly altered mice null p85β, whereas proliferating reduced lacking p85β. Finally, there no significant change T lymphocyte p85 deletions, although anti-CD3-stimulated AKT activation somewhat p85α+/- background. These results indicate decreasing levels different can result some tissues decreased others, supporting model that, proteins are essential class IA signaling, they function inhibitors thus suppress formation.