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Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

ABSTRACT: Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

PROVIDER: PRJNA754401 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15443847_1.fastq.gz	Fastqsanger.gz
	SRR15443847_2.fastq.gz	Fastqsanger.gz
	SRR15443848_1.fastq.gz	Fastqsanger.gz
	SRR15443848_2.fastq.gz	Fastqsanger.gz
	SRR15443849_1.fastq.gz	Fastqsanger.gz

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Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

Project description:Most human cancers demonstrate activated MAPK/ERK pathway signaling as a key tumor initiation step, but the immediate steps of further oncogenic progression are poorly understood due to a lack of appropriate models. Spinal cord differentiation follows caudal elongation in vertebrate embryos; both processes are regulated by a FGF8 gradient highest in neuromesodermal progenitors (NMP), where kinase effectors ERK1/2 maintain an undifferentiated state. FGF8/ERK signal attenuation is necessary for NMPs to progress to differentiation. We show that sustained ERK1/2 activity, using a constitutively active form of the kinase MEK1 (MEK1ca) in the chicken embryo, reproducibly provokes neopasia in the developing spinal cord. Transcriptomic data show that neoplasia not only relies on the maintenance of NMP gene expression, and the inhibition of genes expressed in the differentiating spinal cord, but also on a profound change in the transcriptional signature of the spinal cord cells leading to a complete loss of cell-type identity. MEK1ca expression in the developing spinal cord of the chicken embryo is therefore a tractable in vivo model to identify the critical factors fostering malignancy in ERK-induced tumorigenesis.

2021-08-17 | GSE182072 | GEO

Proteosome-Erk dependent transcriptional events

Project description:Proteosome-Erk dependent transcriptional events

| PRJNA434732 | ENA

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord models early events in ERK-mediated tumorigenesis.

Project description:The MAPK/ERK pathway regulates a variety of physiological cellular functions, including cell proliferation and survival. It is abnormally activated in many types of human cancers in response to driver mutations in regulators of this pathway that trigger tumor initiation. The early steps of oncogenic progression downstream of ERK overactivation are poorly understood due to a lack of appropriate models. We show here that ERK1/2 overactivation in the trunk neural tube of the chicken embryo through expression of a constitutively active form of the upstream kinase MEK1 (MEK1ca), rapidly provokes a profound change in the transcriptional signature of developing spinal cord cells. These changes are concordant with a previously established role of the tyrosine kinase receptor ligand FGF8 acting via the ERK1/2 effectors to maintain an undifferentiated state. Furthermore, we show that MEK1ca-transfected spinal cord cells lose neuronal identity, retain caudal markers, and ectopically express potential effector oncogenes, such as AQP1. MEK1ca expression in the developing spinal cord from the chicken embryo is thus a tractable in vivo model to identify the mechanisms fostering neoplasia and malignancy in ERK-induced tumorigenesis of neural origins.

| S-EPMC8717438 | biostudies-literature

Proteosome-Erk dependent transcriptional events

Project description:Transcriptome analysis of ESCs treated with a proteosome inhibitor (MG132 1μM), with our without ERK activity to measure Erk-dependent changes in transcriptome regulation

2019-08-08 | GSE110877 | GEO

Global expression analysis identified a preferentially NGF-induced transcriptional program regulated by sustained MEK/ERK and AP-1 activation during PC12 differentiation.

2011-11-13 | GSE33639 | GEO

Global expression analysis identified a preferentially NGF-induced transcriptional program regulated by sustained MEK/ERK and AP-1 activation during PC12 differentiation.

Project description:Neuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared to transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 hrs, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially upregulated in response to NGF. PC12 cells that were starved in low serum media for 24 hrs were treated with NGF (50ng/mL) or EGF (25ng/mL) for 2 or 4 hrs, or left untreated. Total RNA for 3 independent biological replicates was extracted and subjected to Affymetrix Rat Gene 1.0ST Arrays. The 69 genes that were preferentially upregulated by NGF compared to EGF met the following criteria: NGF/No treatment log2> 1, FDR p value< 0.01 and NGF/EGF log2> 0.75, FDR p value< 0.01.

2011-11-13 | E-GEOD-33639 | biostudies-arrayexpress

Effect of FGF8 on bovine granulosa cells

Project description:FGF8 induction of immediate-early response genes

2013-10-10 | GSE41489 | GEO

Effect of FGF8 on bovine granulosa cells

Project description:FGF8 induction of immediate-early response genes Cells treated for 2 h vs untreated controls. Three biological replicates

2013-10-10 | E-GEOD-41489 | biostudies-arrayexpress

Fgf8 E18.5 hypomorph versus control mouse fetal lungs

Project description:We set out to look for genome wide gene expression changes due to deficiency of Fgf8 in the lung.

2010-09-20 | GSE22893 | GEO

Transcription profiling of animal caps from Danio rerio embryos expressing GFP or vhnf1 and treated with FGF8 or BSA protein

Project description:Zebrafish embryo animal cap explants were differentiated by injection of vhnf1 mRNA into the one-cell stage embryo, and treatment of excised explants with applied FGF8 protein. To identify unique targets of the combination of vhnf1+FGF8, each factor was applied alone and in combination, and differences in gene expression used to identify unique targets of vhnf1+FGF8.

2007-05-01 | E-MEXP-818 | biostudies-arrayexpress

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