Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oncogenic potential of RAS isoforms in melanocytes

ABSTRACT: We compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. While both NRAS and KRAS activate MAPK signaling, only NRAS enhances MYC activity in these cells. Our data suggests that the activity of specific RAS isoforms is context dependent and provides a possible explanation for the prevalence of NRAS mutations in melanoma.In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways. Keywords: RAS isoforms

ORGANISM(S): Mus musculus

PROVIDER: GSE6194 | GEO | 2006/10/30

SECONDARY ACCESSION(S): PRJNA100677

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Oncogenic potential of RAS isoforms in melanocytes

Project description:We compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. While both NRAS and KRAS activate MAPK signaling, only NRAS enhances MYC activity in these cells. Our data suggests that the activity of specific RAS isoforms is context dependent and provides a possible explanation for the prevalence of NRAS mutations in melanoma.In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways. Keywords: RAS isoforms Common Reference

2010-06-10 | E-GEOD-6194 | biostudies-arrayexpress

Genomic Analysis Reveals Distinct Mechanisms and Functional Classes of SOX10-Regulated Genes in Melanocytes [gene expression]

Project description:We performed ChIP-Seq analysis of SOX10, histone H3 lysine 27 acetylation (H3K27ac) and H3K27 trimethylation (H3K27me3) in melanocytes to profile the genomic binding sites of SOX10 and the chromatin landscape. In parallel, we generated Sox10 haploinsufficient cell lines using gene knockout approaches and conducted microarray gene expression analysis to identify functional gene targets of SOX10 transcriptional regulation in melanocytes. We demonstrate that SOX10 predominantly engages “open” chromatin, binds to melanocyte enhancer elements and plays a central role in transcriptional activation and repression of functionally distinct classes of genes. Furthermore, we identified cis-regulatory sequence motifs of putative co-regulatory transcription factors that define SOX10-activated and SOX10-repressed target genes. Our results uncover novel mechanisms and roles of SOX10 in global transcriptional regulation of diverse regulatory pathways in the melanocyte lineage. These results indicated that SOX10 plays a role in activation and repression of distinct classes of genes. Microarray gene expression analysis in Sox10 haploinsufficient immortal melanocyte cell lines derived from 3-day-old Sox10LacZ/+; Ink4a-Arf null mice. Syngeneic control cells were melan-Ink4a-Arf-1.

2015-07-03 | E-GEOD-69860 | biostudies-arrayexpress

Identification of hypoxia-induced HIF1A targets in melanocytes reveals a molecular profile associated with poor prognosis for melanoma [ChIP-seq]

Project description:ChIP-seq profiling of HIF1A binding in mouse immortalized melanocyte cell line melan-Ink4a-Arf null cells

2017-02-20 | GSE86554 | GEO

LKB1 modulates lung cancer differentiation and metastasis

Project description:Inherited mutation in LKB1 results in the Peutz-Jeghers syndrome (PJS), characterized by intestinal hamartomas and a modestly increased frequency of gastrointestinal and breast cancer1. Somatic inactivation of LKB1 occurs in human lung adenocarcinoma2-4, but its tumor suppressor role in this tissue is unknown. Here we show that somatic Lkb1 deficiency strongly cooperates with somatic K-rasG12D activating mutation to accelerate the development of mouse lung tumorigenesis. Lkb1 deficiency in the setting of K-rasG12D mutation (K-ras Lkb1L/L) was associated with decreased tumor latency and increased tumor aggressiveness including metastasis. Furthermore, tumors from K-ras Lkb1L/L mice demonstrated histologies--squamous, adenosquamous and large cell--not seen with K-rasG12D mutation, Ink4a/Arf inactivation, or p53 inactivation alone or in combination. Experiments in vitro suggest that LKB1 suppresses lung tumorigenesis and progression through both p16INK4a-ARF-p53 dependent and independent mechanisms. These data indicate that LKB1 regulates lung tumor progression and differentiation. Keywords: cancer research

2007-08-28 | GSE6135 | GEO

RNA-seq to investigate impact of treatment of KRAS mutant A549 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib

Project description:KRAS mutation is widely presumed to confer independence from upstream RTK signalling, however emerging evidence from mouse models of lung cancer suggests that ERBB RTKs may amplify signalling through RAS isoforms and participate in mutant RAS-driven lung cancer. This is one of 3 datasets where we examined the transcriptional impact of treatment of KRAS mutant human lung cancer cell lines with the multi-ERBB inhibitor Neratinib

2018-06-01 | E-MTAB-6483 | biostudies-arrayexpress

RNA-seq to investigate impact of treatment of KRAS mutant NCI-H2009 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib

2018-06-01 | E-MTAB-6486 | biostudies-arrayexpress

RNA-seq to investigate impact of treatment of KRAS mutant NCI-H358 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib

2018-06-01 | E-MTAB-6485 | biostudies-arrayexpress

The Ink4a/Arf locus operates as a regulator of the circadian clock modulating RAS activity

Project description:Upon perturbations by RAS and by shBMAL, differential effects on the circadian phenotype were observed in wild type and Ink4a/Arf knockout MEFs which could be reproduced by modelling simulations and correlated with opposing cell cycle fate decisions.

2017-12-08 | E-MTAB-5943 | biostudies-arrayexpress

Transcription profiling of human peripheral blood mononuclear cells WITH a germline NRAS mutation vs controls reveals NRAScauses a novel human autoimmune lymphoproliferative syndrome (ALPS)

Project description:The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization and other signaling networks, and is the most frequent target of activating mutations in cancer. Activating germline mutations of KRAS and HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous and Costello syndrome, but activating germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and causes autoimmunity as well as excessive lymphocyte accumulation, particularly of CD4-, CD8- ab T cells. Mutations in ALPS typically affect CD95 (Fas/APO-1)-mediated apoptosis, one of the extrinsic death pathways involving tumor necrosis factor receptor (TNFR) superfamily proteins, but certain ALPS individuals have no such mutations. We show here that the salient features of ALPS as well as a predisposition to hematological malignancies can be caused by a heterozygous germline Gly13Asp activating mutation of the NRAS oncogene that does not impair CD95-mediated apoptosis. The increase in active, GTP-bound NRAS augments RAF/MEK/ERK signaling which markedly decreases the pro-apoptotic protein BIM and attenuates intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus, germline activating mutations in NRAS differ from other p21 Ras oncoproteins by causing selective immune abnormalities without general developmental defects. Our observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyl-transferase inhibitors (FTIs) should be examined in human autoimmune and lymphocyte homeostasis disorders. Experiment Overall Design: Describes the discovery of a new gene underlying a novel type of autoimmune lymphoproliferative syndrome, and characterizes the mechanisms involved in the pathogenesis of the disease.

2008-04-04 | E-GEOD-7345 | biostudies-arrayexpress

Expression analysis of AOM-induced tumors and serrated tumors in mice

Project description:Abstract: Colonic cancers with a serrated morphology have been proposed to comprise a molecularly distinct tumor entity following an alternative pathway of genetic alterations independently of APC mutations. Here we demonstrate that intestinal cell specific expression of oncogenic K-rasG12D in mice induces serrated hyperplasia, which is characterized by p16ink4a overexpression and induction of senescence. Deletion of Ink4a/Arf in K-rasG12D expressing mice prevents senescence and leads to invasive, metastasizing carcinomas with morphological and molecular alterations comparable to human KRAS mutated serrated tumors. Thus, we suggest that oncogenic K-ras is sufficient to initiate an alternative, serrated pathway to colorectal cancer and hence propose RAS-RAF-MEK signaling apart from APC as an additional gatekeeper in colorectal tumor development.

2010-03-06 | GSE20647 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data