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Title: Differentiation of Mesenchymal Glioblastoma Multiform by Bexarotene      
keywords:
Transcriptome or Gene expression
ID:
PRJNA260057
description:
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Differentiation can attenuate or block tumor growth; thus, phenotypic screenings were performed to search for drugs inducing differentiational morphological changes in mesenchymal recurrent GBM, a temozolomide (TMZ)-resistant brain cancer. Bexarotene, a selective retinoid X receptor agonist, showed strong inhibition of neurospheroidal colony formation and migration of cultured GBM stem cells. Bexarotene decreased nestin expression and significantly increased GFAP expression. Gene expression changes by bexarotene and all-trans retinoic acid (ATRA), a well-known differentiation inducer, were compared. Both drugs largely altered the gene expression pattern into a tumor-ameliorating direction. These drugs increased the gene expression levels of Krüppel-like factor 9 (KLF9), regulator of G-protein signaling 4 (RGS4), growth differentiation factor 15 (GDF15), angiopoietin-like protein 4 (ANGPTL4), and lowered the level of chemokine receptor type 4 (CXCR4). Both drugs also induced a potential oncogene, transglutaminase 2 (TG2), but the fold-change induced by bexarotene was considerably lesser than that by ATRA. Consistently, the TG2 activity in GBM was elevated several folds by ATRA. Because TG2 upregulation is correlated with tumor transformation and resistance, it is important to control its overexpression. Bexarotene does not upregulate TG2 as much as ATRA, and bexarotene showed in vivo tumoricidal effects in a GBM xenograft mouse model. Thus, these findings strongly suggest that bexarotene is more beneficial than ATRA and should be considered as a differentiation therapeutic agent for mesenchymal GBM. Overall design: Mesenchymal GBM cell line (total 12 samples) : (a) Control (0.1% DMSO), (b) 10uM ATRA, (c) 10uM Bexarotene, and (d) 1uM Bexarotene. Each condition has 3 replicates, repectively.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA260057
authentication:
none
authorization:
none
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject