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

Overview

MeSH Major

  • Carcinoma, Hepatocellular
  • Cell Transformation, Neoplastic
  • Intercellular Signaling Peptides and Proteins
  • Liver Neoplasms
  • Phosphatidylinositol 3-Kinases

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.

publication date

  • July 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3204358

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-3399

PubMed ID

  • 20530665

Additional Document Info

start page

  • 5305

end page

  • 15

volume

  • 70

number

  • 13