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Expression profiling of BRAFV600E melanoma cell lines upon RAF inhibition

ABSTRACT: Microarray expression analysis to identify global changes in transcription in response to RAF inhibition. Genes under RAF control were identified in a panel of BRAFV600E tumor cells, following the short-term inhibition of RAF using a pan-RAF kinase inhibitor, PLX4032 (Plexxikon). For comparison with changes in gene expression in response to MEK inhibition using PD0325901 (Pfizer), the following array data was referenced: (http://www.ncbi.nlm.nih.gov/geo/ (accession no. GSE10086)).

ORGANISM(S): Homo sapiens

PROVIDER: GSE20051 | GEO | 2010/07/18

SECONDARY ACCESSION(S): PRJNA124317

REPOSITORIES: GEO

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Expression profiling of BRAFV600E melanoma cell lines upon RAF inhibition

Project description:Microarray expression analysis to identify global changes in transcription in response to RAF inhibition. Genes under RAF control were identified in a panel of BRAFV600E tumor cells, following the short-term inhibition of RAF using a pan-RAF kinase inhibitor, PLX4032 (Plexxikon). For comparison with changes in gene expression in response to MEK inhibition using PD0325901 (Pfizer), the following array data was referenced: (http://www.ncbi.nlm.nih.gov/geo/ (accession no. GSE10086)). Cell lines growing in culture (n=5) were treated with the RAF inhibitor PLX4032 (250nM or 1000nM) or vehicle alone (0.1% DMSO) as control, for eight hours.

2010-07-18 | E-GEOD-20051 | 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 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

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.

2009-02-21 | E-GEOD-10087 | biostudies-arrayexpress

Gene expression profiling of B9 cells in response to two classes of BRAF inhibitors

Project description:Selective RAF inhibitors including vemurafenib (PLX4032) have demonstrated clinical efficacy in mutant BRAF driven metastatic melanoma. The clinical effectiveness of RAF inhibitors depends on near complete abolition of the MAPK pathway output in tumors harboring BRAF mutations. However these compounds paradoxically activate the MAPK pathway in cells bearing oncogenic RAS or elevated upstream receptor signaling. This paradox can promote cellular proliferation and can manifest clinically with progression of secondary malignancies such as cutaneous squamous cell carcinomas (cuSCC). We have identified next generation RAF inhibitors (“paradox breakers”, e.g. PLX7904) that inhibit mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation. In murine cuSCC B9 cells that express the same HRAS mutation prevalent in squamous tumors from patients treated with RAF inhibitors, the first-generation RAF PLX4032 stimulated in vitro and in vivo growth; by contrast the paradox breaker PLX7904 had no effect. Here we compared the gene expression changes in B9 cells treated overnight with PLX4032 and PLX7904.

2015-10-01 | GSE71109 | GEO

A phosphoproteomic comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells, part 2

Project description:. To provide insight into the molecular nature of clinical responses to B-RAF(V600E) and MKK1/2 inhibition, we used quantitative mass spectrometry to characterize the inhibitor-dependent phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor PLX4032 (vemurafenib) and the MKK1/2 inhibitor AZD6244 (selumetinib).. In three replicate experiments, we quantified a total of 23,986 phosphosites on 4,722 proteins. This included 1,317 phosphosites that reproducibly decreased in response to at least one inhibitor.

2016-02-25 | PXD001563 | Pride

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

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

Pan-Raf co-operates with PI3K-dependent signaling and critically contributes to myeloma cell survival independently of mutated RAS

Project description:The most common oncogenic mutations in multiple myeloma (MM) affect N- and K-RAS leading to constitutive activation of RAS-dependent signaling. Signal transduction via RAS, Raf and MAPK has been well described as a canonical pathway. In accordance with this assumption, we showed that the activity of the MEK/ERK module is strictly dependent on pan-Raf activity. However, inhibition of MEK/ERK has no or only minor effects on MM cell survival, whereas oncogenic Ras and pan-Raf critically contribute to survival of multiple myeloma cells. Therefore, we aimed to learn more about Raf-dependent but MEK-independent signaling effectors. We analyzed gene expression profiles in INA-6 cells after either pan-Raf inhibition with SB-590885 or MEK inhibition with PD-325901.

2016-11-21 | GSE75078 | GEO

Genome-wide analysis of RAF inhibition in HCT116 cells in culture

Project description:gene expression profile of HCT116 p53+/+ cells in response to RAF inhibition Total RNA obtained from HCT116 cells treated with or without 10nM SB590885 Gaurisankar, Sa

2016-05-28 | E-GEOD-81973 | biostudies-arrayexpress

Genome-wide analysis of RAF inhibition in HCT116 cells in culture

Project description:gene expression profile of HCT116 p53+/+ cells in response to RAF inhibition Total RNA obtained from HCT116 cells treated with or without 10nM SB590885

2016-05-28 | GSE81973 | GEO

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