Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade

被引：97

作者：

Harir, Noria ^{[2
]}

Boudot, Cedric ^{[2
]}

Friedbichler, Katrin ^{[1
]}

Sonneck, Karoline ^{[3
]}

Kondo, Rudin ^{[3
]}

Martin-Lanneree, Severine ^{[4
,5
]}

Kenner, Lukas ^{[1
,6
]}

Kerenyi, Marc ^{[7
]}

Yahiaoui, Saliha ^{[2
]}

Gouilleux-Gruart, Valerie ^{[2
]}

Gondry, Jean ^{[8
]}

Benit, Laurence ^{[4
,5
]}

Dusanter-Fourt, Isabelle ^{[4
,5
]}

Lassoued, Kaiss ^{[2
]}

Valent, Peter ^{[3
]}

Moriggl, Richard ^{[1
]}

Gouilleux, Fabrice ^{[2
]}

机构：

[1] Ludwig Boltzmann Inst Canc Res, A-1090 Vienna, Austria

[2] Univ Picardie J Verne, Fac Med, INSERM, EMI 351, Amiens, France

[3] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria

[4] Univ Paris 05, Inst Cochin Genet Mol, CNRS, UMR 8104, Paris, France

[5] INSERM, U567, Paris, France

[6] Med Univ Vienna, Dept Pathol, Vienna, Austria

[7] Med Univ Vienna, Div Mol Biol, Dept Med Biochem, Max F Perutz Labs, Vienna, Austria

[8] Ctr Hosp Univ, Ctr Gynecol Obstet, Amiens, France

来源：

BLOOD | 2008年 / 112卷 / 06期

基金：

奥地利科学基金会;

关键词：

D O I：

10.1182/blood-2007-09-115477

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5F) was found to trigger PI3K and Akt activation, and to transform murine bone marrow progenitors into tissue-infiltrating MCs. Primary neoplastic Kit D816V(+) MCs in patients with mastocytosis also displayed activated Stat5, which was found to localize to the cytoplasm and to form a signaling complex with PI3K, with consecutive Akt activation. Finally, the knock-down of either Stat5 or Akt activity resulted in growth inhibition of neoplastic Kit D816V(+) MCs. These data suggest that a downstream Stat5-PI3K-Akt signaling cascade is essential for Kit D816V-mediated growth and survival of neoplastic MCs.

引用

页码：2463 / 2473

页数：11

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