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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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 Common Reference

ORGANISM(S): Mus musculus

SUBMITTER: Karl Dykema

PROVIDER: E-GEOD-6194 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential oncogenic potential of activated RAS isoforms in melanocytes.

Whitwam T T Vanbrocklin M W MW Russo M E ME Haak P T PT Bilgili D D Resau J H JH Koo H-M HM Holmen S L SL

Oncogene 20070205 31

RAS genes are mutated in approximately 30% of all human cancers. Interestingly, there exists a strong bias in favor of mutation of only one of the three major RAS genes in tumors of different cellular origins. NRAS mutations occur in approximately 20% of human melanomas, whereas HRAS and KRAS mutations are rare in this disease. To define the mechanism(s) responsible for this preference in melanocytes, we compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transforme ...[more]

PMID: 17297468

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

2006-10-30 | GSE6194 | GEO

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

Germline NRAS mutation causes a novel human autoimmune lymphoproliferative syndrome

2008-03-21 | GSE7345 | 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

A comprehensive and quantitative interactome of RAS

Project description:We investigated a comprehensive and quantitative interactome of RAS, a protein found to be a driver of many human cancers. This resource identifies interactors of the active form of RAS (nucleotide-dependent) as well as isoform-specific (KRAS, HRAS, and NRAS) interactors of RAS. Several of the proteins identified were confirmed as being important for cancer cell viability and senescence.

2022-10-13 | PXD034847 | Pride

Interrogation of the oncogenic RAS interactomes by BirA* based proximity labeling

Project description:We determined the specific protein interactomes of each RAS isoform (HRAS G12V, NRAS G12V and KRAS G12V) by BirA proximity-dependent biotin identification (BioID) in HEK-HT cells (folder hnk ras). We also determined protein interactomes of KRASG12V (folder: ras1) and HRASG12V (folder: ras2) in PIP5K1A deficient HEK-HT cells.

2018-07-08 | MSV000082583 | MassIVE

RNA sequencing analysis of Nras mutant MEFs

Project description:Purpose: Emerging evidence in the field of RAS biology is beginning to illustrate that RAS mutations are functionally distinct. To elucidate functional differences between NRAS mutants we performed RNA-sequencing on mouse embryonic fibroblasts (MEFs) expressing different NRAS codon 61 variants from the endogenous gene locus Methods: MEFs were isolated from Tyr::CRE-ERT2 LSL-Nras mouse models containing different Nras variants in the endogeous gene locus. NRAS expression was induced in MEFs using an Adenoviral Cre delivery system. RNA was isolated from MEFs six days post-NRAS induction and submitted for RNA-sequencing Results: Differential expression and gene set enrichment analysis (GSEA) between NRAS variants revealed enrichment of transcripts associated with cellular proliferation between all mutant Nras alleles versus wild-type Nras. Further, MEFs expressing NRAS mutants capable of driving melanoma formation were enriched for transcripts associated with RAS-MYC signaling axis. Conclusion: While all NRAS mutants are capable of enhancing cellular proliferation versus wild-type NRAS, the melanomagenic potential of these mutants correlates with the ability to enhance activation of the RAS-MYC signaling axis

2022-04-30 | GSE162124 | GEO

Deciphering KRAS and NRAS mutated clones dynamics in MLL-AF4 pediatric leukemia by ultra deep sequencing analysis

Project description:We studied the KRAS and NRAS mutational status in pediatric MLL-AF4+ leukemia patients by means of ultra deep amplicon sequencing. The gene expression profiles of RAS wild type and RAS mutated patients were investigated by gene expression analysis. We showed that mutated patients were characterized by a RAS related expression signature.

2016-10-04 | GSE77416 | GEO

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