Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of glioblastoma primary culture treated with TGF-beta receptor inhibition.

ABSTRACT: TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma. Differential gene expression analysis of patient-derived primary cultured glioblastoma cells treated with the TGF-beta receptor inhibitor, LY2109761 11 patient-derived cell cultures from 11 patients were treated with 2microM of the TGF-beta receptor inhibitor, LY2109761, for 3 hours or left untreated and RNA was isolated and microarray analysis was performed

ORGANISM(S): Homo sapiens

SUBMITTER: Joan Seoane

PROVIDER: E-GEOD-23935 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.

Anido Judit J Sáez-Borderías Andrea A Gonzàlez-Juncà Alba A Rodón Laura L Folch Gerard G Carmona Maria A MA Prieto-Sánchez Rosa M RM Barba Ignasi I Martínez-Sáez Elena E Prudkin Ludmila L Cuartas Isabel I Raventós Carolina C Martínez-Ricarte Francisco F Poca M Antonia MA García-Dorado David D Lahn Michael M MM Yingling Jonathan M JM Rodón Jordi J Sahuquillo Juan J Baselga José J Seoane Joan J

Cancer cell 20101201 6

Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF-β inhibitors, currently under clinical development, target the GIC compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF-β inhibition, which include inhibitors of DNA-binding protein (Id)-1 and -3 transcription factors. We have identified a cell population enriched ...[more]

PMID: 21156287

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Project description:Cashmere, a fiber of high economic value, is produced by secondary hair follicles (SHFs), whose growth depends on the proliferation and apoptosis of SHF-derived dermal papilla cells (SHF-DPCs). All-trans retinoic acid (ATRA), a metabolite of vita min A, has shown inconsistent effects on hair follicle biology, with reports of both inhibition and stimulation. To clarify the role of ATRA in follicular development, we investigated its effects on the proliferation and apoptosis of in vitro–cultured SHF-DPCs isolated from Capra hircus (Albas cashmere goats). SHF-DPCs were obtained from scapular skin, and the optimal ATRA concentration (10−4 M) and treatment duration (24 h) were identified using Cell Counting Kit-8, 5-ethynyl-2′ deoxyuridine, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Cells were then assigned to an ATRA-treated group (10−4 M) or a control group. Proliferation, apoptosis, and cell cycle progression were evaluated, fol lowed by transcriptome sequencing. Transcriptomic analysis indicated enrich ment of the transforming growth factor-β (TGF-β) signaling pathway. Therefore, mRNA and protein levels of TGF-β2—a follicle growth–related regulator—and Smad2/3 phosphorylation were examined. The TGF-β type I/II receptor inhibitor LY2109761 was used to further validate the involvement of this pathway. ATRA inhibited SHF-DPC proliferation by inducing G1-phase cell cycle arrest and pro moted apoptosis by upregulating Bax expression while downregulating Bcl-2 protein expression. Transcriptomic analysis showed that ATRA upregulated TGFβ2 expression in SHF-DPCs. Gene Ontology analysis revealed enrichment of genes related to proliferation and apoptosis, such as “cell migration” and “cell cycle.” Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the TGF β signaling pathway as a major regulatory target. Treatment with LY2109761 par tially reversed ATRA-induced reductions in proliferation, increases in apoptosis, and elevations in Smad2/3 phosphorylation. Overall, ATRA inhibits proliferation and promotes apoptosis in SHF-DPCs, likely through the TGF-β2/Smad2/3 path way. These findings provide novel insights into ATRA-mediated regulation of hair growth and offer a theoretical basis for future research on cashmere goat SHF development.

Dataset Information

Transcription profiling of glioblastoma primary culture treated with TGF-beta receptor inhibition.

Publications

TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.

Similar Datasets

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