The phosphoinositide 3-kinase regulatory subunit p85α can exert tumor suppressor properties through negative regulation of growth factor signaling

Cullen M. Taniguchi, Jonathon Winnay, Tatsuya Kondo, Roderick T. Bronson, Alexander Guimaraes, José O. Alemán, Ji Luo, Gregory Stephanopoulos, Ralph Weissleder, Lewis C. Cantley, C. Ronald Kahn

Research output: Contribution to journalArticle

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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 liverspecific 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.

Original languageEnglish (US)
Pages (from-to)5305-5315
Number of pages11
JournalCancer Research
Volume70
Issue number13
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

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1-Phosphatidylinositol 4-Kinase
Intercellular Signaling Peptides and Proteins
Liver
Neoplasms
Gene Deletion
Liver Neoplasms
Urinary Bladder Neoplasms
Ovarian Neoplasms
Hepatocellular Carcinoma
Lung Neoplasms
Prostatic Neoplasms
Carcinogenesis
Insulin
Pathology
Neoplasm Metastasis
Gene Expression
Lung
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The phosphoinositide 3-kinase regulatory subunit p85α can exert tumor suppressor properties through negative regulation of growth factor signaling. / Taniguchi, Cullen M.; Winnay, Jonathon; Kondo, Tatsuya; Bronson, Roderick T.; Guimaraes, Alexander; Alemán, José O.; Luo, Ji; Stephanopoulos, Gregory; Weissleder, Ralph; Cantley, Lewis C.; Kahn, C. Ronald.

In: Cancer Research, Vol. 70, No. 13, 01.07.2010, p. 5305-5315.

Research output: Contribution to journalArticle

Taniguchi, CM, Winnay, J, Kondo, T, Bronson, RT, Guimaraes, A, Alemán, JO, Luo, J, Stephanopoulos, G, Weissleder, R, Cantley, LC & Kahn, CR 2010, 'The phosphoinositide 3-kinase regulatory subunit p85α can exert tumor suppressor properties through negative regulation of growth factor signaling', Cancer Research, vol. 70, no. 13, pp. 5305-5315. https://doi.org/10.1158/0008-5472.CAN-09-3399
Taniguchi, Cullen M. ; Winnay, Jonathon ; Kondo, Tatsuya ; Bronson, Roderick T. ; Guimaraes, Alexander ; Alemán, José O. ; Luo, Ji ; Stephanopoulos, Gregory ; Weissleder, Ralph ; Cantley, Lewis C. ; Kahn, C. Ronald. / The phosphoinositide 3-kinase regulatory subunit p85α can exert tumor suppressor properties through negative regulation of growth factor signaling. In: Cancer Research. 2010 ; Vol. 70, No. 13. pp. 5305-5315.
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