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Expression data from BRAFV600E A375 melanoma cells treated with vehicle or vemurafenib

ABSTRACT: Vemurafenib is a BRAF inhibitor with specificity for the most common BRAF mutant encountered in melanomas (BRAFV600E). Vemurafenib suppresses the proliferation of BRAF mutant human melanoma cells by suppressing downstream activation of the MEK/ERK mitogen activated protein kinases. We used microarrays to examine the transcriptional response of a vemurafenib-sensitive BRAFV600E human melanoma cell line (A375) to vemurafenib in order to further delineate the mechanisms by which BRAFV600E drives cell proliferation and energy metabolism in human melanoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42872 | GEO | 2014/05/20

SECONDARY ACCESSION(S): PRJNA183688

REPOSITORIES: GEO

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Expression data from BRAFV600E A375 melanoma cells treated with vehicle or vemurafenib

Project description:Vemurafenib is a BRAF inhibitor with specificity for the most common BRAF mutant encountered in melanomas (BRAFV600E). Vemurafenib suppresses the proliferation of BRAF mutant human melanoma cells by suppressing downstream activation of the MEK/ERK mitogen activated protein kinases. We used microarrays to examine the transcriptional response of a vemurafenib-sensitive BRAFV600E human melanoma cell line (A375) to vemurafenib in order to further delineate the mechanisms by which BRAFV600E drives cell proliferation and energy metabolism in human melanoma. BRAFV600E A375 human melanoma cells were treated with vehicle (0.1% DMSO) or 10 uM vemurafenib for 24 h after which total RNA was extracted. Cells were prepared and RNA was extracted in 3 separate batches (three different cell stocks on three separate days) providing three independent replicates (n=3). Paired replicates (prepared from the same stock of cells on the same day) are denoted by A, B and C.

2014-05-20 | E-GEOD-42872 | biostudies-arrayexpress

Gene expression profiling of isogenic malignant melanoma A375-BRAFV600E/NRASQ61 and A375-BRAFV600E/NRASQ61K cell lines

Project description:BRAF-inhibitor (BRAFi)-resistance compromises long term survivorship of malignant melanoma patients, and mutant NRAS is a major mediator of BRAFi-resistance. We have employed NanoString nCounterTM transcriptomic analysis of isogenic human malignant melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAFV600E/NRASQ61 versus BRAFi-resistant A375-BRAFV600E/NRASQ61K), identifying modulation of specific gene expression networks as a function of NRASQ61K-status.

2021-09-23 | GSE184633 | GEO

A four-arm study of A375 melanoma cell line-derived xenograft tumors in NSG mice treated with Vemurafenib and CB839

Project description:Melanoma is a rare but deadly form of skin cancer, which is often treated with BRAF inhibitors such as Vemurafenib (referred to as PLX4032). Whilst Vemurafenib prolongs the survival of patients, BRAF inhibitor resistance inevitably occurs in most cases. Previous studies demonstrated that metabolic rewiring occurs in BRAF inhibitor resistance and causes dependence on glutamine. To investigate whether this vulnerability could be exploited with clinically relevant drugs, we used the BRAF inhibitor, Vemurafenib, and the glutaminase imhibitor, CB839 to treat A375-derived melanoma xenografted tumors. We showed that whilst CB839 did not significantly affect the growth of A375-derived tumors compared to those given a vehicle, the addition of CB839 to Vemurafenib treatment had a significant anti-tumor effect. Tumors were taken at the endpoint (Max tumor length 15mm) from the 6 mice in each treatment group and cut into fragments and stored in RNAlater for RNAseq analysis. RNA extraction was performed on 1-3 fragments per tumor to make up 200-300mg of tissue.

2023-04-07 | E-MTAB-12811 | biostudies-arrayexpress

Gene expression of the A375 melanoma cell line treated with RAF inhibitors Vemurafenib and time-course with EGF stimulation during Vemurafenib RAF inhibitor treatment alone or with the MEK inhibitor Cobimetinib

Project description:We treated for 24 hours the BRAF-V600E melanoma cell line A375 with 7 doses of the RAF inhibitor Vemurafenib and, in a second experimental desing, we treated for 24 hours the BRAF-V600E melanoma cell line A375 with Vemurafenib (1 uM) alone or in combination with the MEK inhibitor Cobimetinib (1 uM) and subsequently stimulated with EGF in a time-course of 7 time points for up to 8 hours (0, 0.5, 1, 2, 3, 4, 8 hours).

2020-10-19 | GSE127988 | GEO

Ezrin inhibition overcomes acquired resistance to vemurafenib in BRAFV600E-mutated colon cancer and melanoma cells in vitro

Project description:In spite of the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel pharmacological strategies for BRAF-mutated mCRC. The aim of this study was to identify novel protein candidates involved in acquired resistance to BRAFV600E inhibitor vemurafenib in BRAFV600E-mutated colon cancer cells using an integrated proteomics approach. Our study suggests a role of ezrin in acquired resistance to vemurafenib in colon cancer and melanoma cells carrying BRAFV600E mutation and supports further pre-clinical and clinical studies to explore the benefits of combined BRAF inhibitors and actin-targeting drugs as a potential therapeutic approach for BRAFV600E-mutated cancers.

2023-08-29 | PXD042499 | Pride

Homo sapiens strain:A375 BRAFV600E melanoma clones with acquired resistance to vemurafenib

Project description:Homo sapiens strain:A375 BRAFV600E melanoma clones with acquired resistance to vemurafenib

| PRJNA77989 | ENA

Concomitant BCORL1 and BRAF mutations in vemurafenib-resistant melanoma cells

Project description:BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current front-line therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAFV600E locus, and a missense point mutation of the transcriptional repressor BCORL1, in vemurafenib-resistant A375 melanoma cells. Functional data confirmed that truncated p47BRAFV600E and mutant BCORL1Q1076H both contribute to resistance. Interestingly, either endogenous BCORL1 silencing or ectopic BCORL1Q1076H expression mimicked the effects of a CRISPR/Cas9-edited BCORL1Q1076H locus, suggesting a change-of-function mutation. Transcriptomic data confirmed this hypothesis. Finally, we show that the pan-RAF inhibitor sorafenib is not affected by expression of BRAF deletion variant and effectively synergizes with vemurafenib to block resistant cells, suggesting a possible intervention for this class of mutants.

2018-11-27 | GSE107370 | GEO

A new ALK isoform transported by extracellular vesicles confers drug resistance to vemurafenib in A375 melanoma cells

Project description:Despite the successful use of drugs targeting the MAPK signaling pathway and immunotherapy in melanoma, the majority of patients with metastatic disease still undergo disease progression indicating a gradual development of therapy resistance. In the present study, microarray analyses were performed on BRAF inhibitor sensitive melanoma cells A375 and corresponding vemurafenib (PLX4032) - resistant cells A375_X1 to describe changes in the transcriptome that might play a role in drug resistance. For each cell line the microarray experiment was performed in duplicates.

2019-02-28 | E-MTAB-6596 | biostudies-arrayexpress

Gene expression in Vemurafenib-treated A375 and A2058 melanoma cell lines

Project description:Human melanoma cell line A375 and A2058 were incubated with DMSO (control group) or Vemurafenib (1 μM in DMSO) for 72 hours. Total RNA was isolated with Qiagen RNA isolation kit; 1.5 μg of total RNA was used as template for cDNA synthesis.

2015-12-02 | GSE52882 | GEO

Microarray expression data of A375 eIF4B-knockout (KO; KO/LacZ) and eIF4B-rescued (KO/eIF4B) cells with or without vemurafenib treatment

Project description:Activating Transcription Factor 4 (ATF4) is a key transcription factor of the integrated stress response, which assists cells to survive in response to tumor microenvironmental and therapeutic stresses. BRAF inhibitors, such as vemurafenib, are also known to induce ATF4 in BRAF-mutated melanoma cells, but the mechanisms of ATF4 induction are not fully elucidated. Here, we show that ATF4 expression can be upregulated by eIF4B (eukaryotic initiation factor 4B) in BRAF-mutated A375 cells. In fact, knockout (KO) of eIF4B hindered ATF4 induction as well as ATF4 translation mechanism under vemurafenib treatment, which were effectively recovered by rescue of eIF4B. Transcriptome analysis revealed that eIF4B KO selectively affected ATF4-target gene expression among gene expression altered by vemurafenib. Our results indicate that eIF4B can contribute to cellular stress adaptation by regulating ATF4 expression.

2021-08-13 | GSE179452 | GEO

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