کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963653 1058486 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Abnormal elevated PTEN expression in the mouse antrum of a model of GIST KitK641E/K641E
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Abnormal elevated PTEN expression in the mouse antrum of a model of GIST KitK641E/K641E
چکیده انگلیسی

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)P3, 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. KitK641E knock-in mice, resulting in the substitution of a Lys by Glu at position 641 of Kit. In homozygous KitK641E 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 KitK641E 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 KitK641E 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 KitK641E mice might serve as a feedback mechanism to limit PI 3-kinase activation downstream of Kit in a context of oncogenic mutation.


► Both SHIP2 and PTEN are expressed in antrum of a mouse model of GIST KitK641E knock-in mice.
► A large increase in PTEN expression in antrum in KitK641E homozygous mice was observed as compared to wild type.
► In the human GIST882 imatinib sensitive cell line, both PTEN and SHIP2 were expressed and showed, in part, a nuclear localization.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 23, Issue 11, November 2011, Pages 1857–1868
نویسندگان
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