BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model.

ABSTRACT:

Purpose

BRAF is frequently activated by gene fusion or point mutation in pilocytic astrocytoma, the most common pediatric brain tumor. We investigated the functional effect of constitutive BRAF activation in normal human neural stem and progenitor cells to determine its role in tumor induction in the brain.

Experimental design

The constitutively active BRAF(V600E) allele was introduced into human neurospheres, and its effects on MAPK (mitogen-activated protein kinase) signaling, proliferation, soft agarose colony formation, stem cell phenotype, and induction of cellular senescence were assayed. Immunohistochemistry was used to examine p16(INK4a) levels in pilocytic astrocytoma.

Results

BRAF(V600E) expression initially strongly promoted colony formation but did not lea

SUBMITTER: Raabe EH 

PROVIDER: S-EPMC4086658 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature