The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling
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Stephanopoulos_Phosphoinositide 3-kinase.pdf
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Author(s)
Taniguchi, Cullen M.
Winnay, Jonathon
Kondo, Tatsuya
Bronson, Roderick T.
Guimaraes, Alexander R.
Aleman, Jose O.
Luo, Ji
Stephanopoulos, Gregory
Weissleder, Ralph
Cantley, Lewis C.
Date Issued
June 2010
Journal
Cancer Research
Publisher
American Association for Cancer Research
Citation
Taniguchi, C. M., J. Winnay, T. Kondo, R. T. Bronson, A. R. Guimaraes, J. O. Aleman, J. Luo, et al. The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties Through Negative Regulation of Growth Factor Signaling. Cancer Research 70, no. 13 (June 30, 2010): 5305-5315.
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Author's final manuscript
Abstract
Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive and negative effects on signaling. Expression of Pik3r1, the gene encoding p85, is decreased in human prostate, lung, ovarian, bladder, and liver cancers, consistent with the possibility that p85 has tumor suppressor properties. We tested this hypothesis by studying mice with a liver-specific deletion of the Pik3r1 gene. These mice exhibited enhanced insulin and growth factor signaling and progressive changes in hepatic pathology, leading to the development of aggressive hepatocellular carcinomas with pulmonary metastases. Liver tumors that arose exhibited markedly elevated levels of phosphatidylinositol (3,4,5)-trisphosphate, along with Akt activation and decreased PTEN expression, at both the mRNA and protein levels. Together, these results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues. Cancer Res; 70(13); 5305–15.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1158/0008-5472.CAN-09-3399
