Gene expression data from PNU 96415E treated human glioblastoma derived neural stem cells (GNS)

ABSTRACT: Glioblastomas grow in a rich neurochemical mileu, but targeting neurochemical signaling as a potential therapeutic avenue for these incurable tumors has been underexplored. Thus, we probed patient derived glioblastoma stem cells with a focused library of neurochemicals, to identify new therapeutic targets. Dopaminergic, serotonergic and cholinergic pathways were found to be active against glioblastoma. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited glioblastoma growth in vitro and in vivo, in addition to showing synergistic effect with temozolomide. Small molecule or genetic antagonism of DRD4 suppressed ERK1/2 signaling and impaired autophagic flux causing accumulation of autophagic vacuoles and ubiquitinated proteins, associated with G0/G1 cell cycle arrest. These data suggest a new mechanism for treating glioblastoma through modulating dopamine DRD4 signaling. We used Affymetrix microarrays to characterize the mechanism of action for dopamine receptor D4 antagonist (PNU 96415E) in human glioblastoma derived neural stem cells. We treated the human glioblastoma derived neural stem cells (GNS cells) with PNU 96415E for period of 0h, 24h and 48h and extracted RNA for hybridaization on Affymetrix microarrary (Human gene 1.0 ST array) on two GNS lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Dirks 

PROVIDER: E-GEOD-62714 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress