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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human cell lines in culture (n=12) and murine xenografts (n=2) were treated with the MEK inhibitor PD0325901 or vehicle alone as controlPaired MEK inhibited and control

ABSTRACT: This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a panel of V600E BRAF and RTK-activated tumor cells and xenografts, using short-term inhibition of ERK activity using the MEK inhibitor PD0325901 (Pfizer). Experiment Overall Design: Cell lines growing in culture (n=12) and murine xenografts (n=2) were treated with the MEK inhibitor PD0325901 or vehicle alone as control. Paired analysis of MEK inhibited to control samples was performed for two groups of tumor cells, V600E BRAF and RTK.

ORGANISM(S): Homo sapiens

SUBMITTER: Christine Anne Pratilas

PROVIDER: E-GEOD-10087 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of human panel of V600E BRAF and RTK-activated tumor cells and xenografts upon MEK inhibition

Project description:This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a panel of V600E BRAF and RTK-activated tumor cells and xenografts, using short-term inhibition of ERK activity using the MEK inhibitor PD0325901 (Pfizer). Experiment Overall Design: Cell lines growing in culture (n=12) and murine xenografts (n=2) were treated with the MEK inhibitor PD0325901 or vehicle alone as control. Paired analysis of MEK inhibited to control samples was performed for two groups of tumor cells, V600E BRAF and RTK. Time course analysis was performed on one representative cell line in order to first determine the optimal time point to detect changes in all cell lines.

2009-02-20 | E-GEOD-10086 | biostudies-arrayexpress

Paired MEK inhibited and control

2009-02-11 | GSE10087 | GEO

Expression profiling of V600E BRAF and RTK-activated cells upon MEK inhibition

2009-02-11 | GSE10086 | GEO

Transcription profiling of human SkMel-28 cells growing in culture treated with the MEK inhibitor PD0325901 for 2, 8, or 24 hours time course of MEK inhibition

Project description:This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a representative V600E BRAF cell line as a function of time following exposure to a small molecule inhibitor of MEK. Experiment Overall Design: SkMel-28 cells growing in culture were treated with the MEK inhibitor PD0325901 for 2, 8, or 24 hours. Changes in RNA compared to reference (time =0) were measured using microarray analysis.

2009-02-21 | E-GEOD-10088 | biostudies-arrayexpress

Time course of MEK inhibition

Project description:This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a representative V600E BRAF cell line as a function of time following exposure to a small molecule inhibitor of MEK. Keywords: Time course

2009-02-11 | GSE10088 | GEO

Transcriptional responses to GSK3 inhibitor and MEK inhibitor on 2i-adapted mouse embryonic stem cells

Project description:The objective of this study was to investigate the roles of GSK3 inhibitor CHIR99021 and MEK inhibitor PD0325901 on 2i-adapted mouse embryonic stem cells (ESCs) in serum-free conditions.Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and β-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and β-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by β-catenin entry into this complex. Wnt pathway stimulation also triggers β-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to mouse promote ESC differentiation. Triplicates of mouse embryonic stem cells cultured under the following conditions: 1) CHIR99021+PD0325901+LIF; 2) CHIR99021+PD0325901; 3) CHIR99021; 4) PD0325901; 5) DMSO

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Identify the downstream targets of Stat3 by using an engineered mouse ES cell line treated with GCSF and LIF plus PD0325901

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2012-06-13 | E-GEOD-38719 | biostudies-arrayexpress

MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors, despite transcriptional feedback onto ERK.

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2012-12-28 | GSE41747 | GEO

Enhancer Remodeling During Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacological Targeting of the P-TEFb Complex (Exome-seq)

Project description:Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment. In preclinical models MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation and p300 that drives transcriptional adaptation. Inhibition of P-TEFb associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts and syngeneic mouse TNBC models. Pharmacological targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance.

2017-01-20 | GSE87423 | GEO

Enhancer Remodeling During Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacological Targeting of the P-TEFb Complex (RNA-seq)

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