The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling
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...
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| Language: | en_US |
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American Association for Cancer Research
2013
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| Online Access: | http://hdl.handle.net/1721.1/79358 https://orcid.org/0000-0001-6909-4568 |
| _version_ | 1810992115854868480 |
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| author | 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. Kahn, C. Ronald |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering 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. Kahn, C. Ronald |
| author_sort | Taniguchi, Cullen M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:04:28Z |
| format | Article |
| id | mit-1721.1/79358 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:04:28Z |
| publishDate | 2013 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/793582022-10-01T12:53:45Z The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling 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. Kahn, C. Ronald Massachusetts Institute of Technology. Department of Chemical Engineering Stephanopoulos, Gregory Aleman, Jose O. 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. National Institutes of Health (U.S.) (NIH grant DK33201) National Institutes of Health (U.S.) (NIH grant DK55545) Joslin Diabetes Center (Joslin Diabetes and Endocrinology Research Center grant DK34834) Joslin Diabetes Center (Joslin Diabetes and Endocrinology Research Center grant GM41890) Joslin Diabetes Center (Joslin Diabetes and Endocrinology Research Center grant CA089021) Southern Association for Institutional Research (grant 2U24CA092782-07) American Diabetes Association (Medical Scholars Award) Harvard Medical School (Medical Scientist Training Program Scholarship) 2013-06-20T19:34:24Z 2013-06-20T19:34:24Z 2010-06 2010-04 Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 http://hdl.handle.net/1721.1/79358 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. https://orcid.org/0000-0001-6909-4568 en_US http://dx.doi.org/10.1158/0008-5472.CAN-09-3399 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | 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. Kahn, C. Ronald The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title | The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title_full | The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title_fullStr | The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title_full_unstemmed | The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title_short | The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling |
| title_sort | phosphoinositide 3 kinase regulatory subunit p85 can exert tumor suppressor properties through negative regulation of growth factor signaling |
| url | http://hdl.handle.net/1721.1/79358 https://orcid.org/0000-0001-6909-4568 |
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