Abnormal elevated PTEN expression in the mouse antrum of a model of GIST KitK641E/K641E

Laurence Deneubourg, Sebastian Ralea, Petra Gromova, Ramon Parsons, Jean Marie Vanderwinden, Christophe Erneux

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4 Scopus citations


Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 85% of GISTs harbor activating mutations of the KIT or PDGFRA receptor tyrosine kinases. PTEN and SHIP2 are major phosphatases that dephosphorylate PI(3,4,5)P 3, one of the intracellular signal pathways downstream of KIT. PTEN is an important tumor suppressor, whereas the involvement of SHIP2 in cancer has been proposed based essentially on cell line studies. We have used a mouse model of GIST, i.e. Kit K641E knock-in mice, resulting in the substitution of a Lys by Glu at position 641 of Kit. In homozygous Kit K641E mice, PTEN-immunoreactivity (ir) in antrum was found in the hyperplastic Kit-ir layer. The same localization was found for SHIP2. Western blot analysis in antrum showed a large increase in PTEN expression in Kit K641E homozygous mice as compared to wild type. In contrast, SHIP2 expression was not affected between the two genotypes. Erk1, but not PKB, phosphorylation appears to be upregulated in Kit K641E homozygous mice. In the human GIST882 imatinib sensitive cell line, both PTEN and SHIP2 were expressed and showed, in part, a nuclear localization. The upregulation of PTEN in antrum in Kit K641E mice might serve as a feedback mechanism to limit PI 3-kinase activation downstream of Kit in a context of oncogenic mutation.

Original languageEnglish
Pages (from-to)1857-1868
Number of pages12
JournalCellular Signalling
Issue number11
StatePublished - Nov 2011
Externally publishedYes


  • GIST
  • Inositol 5-phosphatase
  • KIT
  • PTEN
  • Phosphatidylinositol metabolism
  • SHIP2
  • Signal transduction


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