Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Harir N 

PROVIDER: S-EPMC2532813 | biostudies-other | 2008 Sep

REPOSITORIES: biostudies-other

altmetric image

Publications


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 mastocyto  ...[more]

Similar Datasets

| S-EPMC5389679 | biostudies-literature
| S-EPMC3057865 | biostudies-other
| S-EPMC4284665 | biostudies-literature
| S-EPMC6037300 | biostudies-literature
| S-EPMC2964112 | biostudies-literature
| S-EPMC5629373 | biostudies-literature
| S-EPMC5730340 | biostudies-literature
2023-03-10 | PXD033889 | Pride
| S-EPMC3072881 | biostudies-literature
| S-EPMC4380442 | biostudies-literature