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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2008

Authors: Harir, N; Boudot, C; Friedbichler, K; Sonneck, K; Kondo, R; Martin-Lannerée, S; Kenner, L; Kerenyi, M; Yahiaoui, S; Gouilleux-Gruart, V; Gondry, J; Bénit, L; Dusanter-Fourt, I; Lassoued, K; Valent, P; Moriggl, R; Gouilleux, F

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

Source: Blood (112), 6 2463-2473.

Authors Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard

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 (cS5(F)) 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.

Keywords Pubmed: Animals
Bone Marrow Cells
Case-Control Studies
Cell Proliferation
Hematopoietic Stem Cells
Leukemic Infiltration
MAP Kinase Signaling System*
Mastocytosis, Systemic/pathology*
Mutation, Missense
Phosphatidylinositol 3-Kinases/metabolism*
Proto-Oncogene Proteins c-akt/metabolism
Proto-Oncogene Proteins c-kit/genetics
Proto-Oncogene Proteins c-kit/physiology*
STAT5 Transcription Factor/metabolism*

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