Transcriptionally inactive ATF2 variant drives melanomagenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA320278 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3332284.fastq.gz | Fastqsanger.gz | |||
| SRR3332285.fastq.gz | Fastqsanger.gz | |||
| SRR3332286.fastq.gz | Fastqsanger.gz | |||
| SRR3332287.fastq.gz | Fastqsanger.gz | |||
| SRR3332288.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression.
2016-05-02 | GSE81013 | GEO
Project description:Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression.
2016-04-29 | GSE79917 | GEO
Project description:Transcriptionally inactive ATF2 variant drives melanomagenesis [Array]
| PRJNA320281 | ENA
Project description:Transcriptionally inactive ATF2 variant drives melanomagenesis [Seq]
| PRJNA317371 | ENA
Project description:Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2(?8,9)) promotes development of melanoma in mouse models. Atf2(?8,9)-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2(?8,9), we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2(SV5)) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2(SV5) expression is elevated in human melanoma specimens and is associated with poor prognosis. These findings point to an oncogenic function for ATF2 in melanoma development that appears to be independent of its transcriptional activity.
| S-EPMC4889472 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-05-02 | GSE81014 | GEO
Project description:primary melanocytes from WT and ATF2 mutant (transcriptionally inactive) mice expressing the mutant N-ras transgene were prepared and assessed for changes in gene expression when maintained under normoxia and hypoxia growth conditions. 12 mouse melanocyte samples were analyzed during normoxia and hypoxia, with different ATF2 genotypes. The pivotal samples are represented as duplicates. Treatment of tamoxifen was used to induce recombination and expression of the mutant ATF2 (inducible Cre). Doxycyclin was used to induce expression of mutant N-Ras transgene.
2010-08-30 | E-GEOD-23860 | biostudies-arrayexpress
Project description:primary melanocytes from WT and ATF2 mutant (transcriptionally inactive) mice expressing the mutant N-ras transgene were prepared and assessed for changes in gene expression when maintained under normoxia and hypoxia growth conditions.
2010-08-30 | GSE23860 | GEO
Project description:Effective therapy for malignant melanoma, the leading cause of death from skin cancer, remains an area of significant unmet need in oncology. Increased expression of PKC? in advanced metastatic melanoma, results in the phosphorylation of the transcription factor ATF2 on threonine 52, which causes its nuclear localization and confers its oncogenic activities. The nuclear-to-mitochondrial translocation of ATF2 following genotoxic stress promotes apoptosis, a function that is largely lost in melanoma cells, due to its confined nuclear localization. Therefore, promoting the nuclear export of ATF2, which sensitizes melanoma cells to apoptosis, offers a novel therapeutic modality. We conducted a pilot high-throughput screen of 3,800 compounds to identify small molecules that promote melanoma cell death by inducing the cytoplasmic localization of ATF2. For this specific gene expression analysis experiment, we subjected WM793 melanoma cells to treatment with DMSO- or 10µM SBI-0087702 for 24 h. RNA was harvested and subjected to microarray analyses using the Illumina Human HT-12 v4 BeadChip. Raw microarray data were normalized using the lumi package in R (variant stabilizing transformation followed by quantile normalization). Subsequent variant-stabilized, normalized microarray values were sorted by fold-change values and subjected to a 1.5-fold-change cut-off threshold. The fold-change-ranked gene list was subjected to gene ontological enriched functional network clustering using the Ingenuity (IPA) gene ontology platform.
2012-12-28 | E-GEOD-43135 | biostudies-arrayexpress
Project description:In order to identify transcriptional targets of ATF2, we used a recombinant adenovirus to express constitutively active ATF2 in murine hepatoblasts. Expression of GFP was the control condition. Total RNA was harvested from cells 8 hours post infection. Reverse transcription was performed using Ovation Pico WTA kit (NuGen, 3300-12). Labelling, Encore Biotin Module (NuGen, 4200-12) three replicates GFP control and C2ATF2
2013-11-10 | E-GEOD-50530 | biostudies-arrayexpress