期刊
BLOOD
卷 112, 期 6, 页码 2463-2473出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-09-115477
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资金
- Association de la Recherche contre le Cancer (ARC)
- Ligue contre le Cancer (Comite du Nord/Pas de Calais/Picardie)
- Conseil Regional de Picardie
- Fondation de France
- Fonds zur Forderung der Wissenschaftlichen Forschung in Osterreich (FWF) [P17205-B14, SFB F28]
- Cent pour Sang la Vie
- French and Algerian Ministry for Research and Technology
- ARC
- Austrian Science Fund (FWF) [F 2807] Funding Source: researchfish
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.
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