期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：29
页码：10238-10243
DOI：10.1073/pnas.0504378102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mice with heterozygous deletion of the PTEN tumor suppressor gene develop a range of epithelial neoplasia as well as lymphoid hyperplasia. Previous studies suggest that PTEN suppresses tumor formation by acting as a phosphoinositide phosphatase to limit signaling by phosphoinositide 3-kinase (PI3K). Here, we examined the effect of deleting various regulatory subunits of PI3K (p85{alpha} and p85{beta}) on epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice. Interestingly, we found the loss of one p85{alpha} allele with or without the loss of p85{beta} led to increased incidence of intestinal polyps. Signaling downstream of PI3K was enhanced in the PTEN+/-p85{alpha}+/-p85{beta}-/- polyps, as judged by an increased fraction of both cells with cytoplasmic staining of the transcription factor FKHR and cells with positive staining for the proliferation marker Ki-67. In contrast, the incidence of prostate intraepithelial neoplasia was not significantly altered in PTEN+/- mice heterozygous for p85{alpha} or null for p85{beta
