Endogenous RAC1 P29S in mouse melanoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA485295 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7663750_1.fastq.gz | Fastqsanger.gz | |||
| SRR7663750_2.fastq.gz | Fastqsanger.gz | |||
| SRR7663751_1.fastq.gz | Fastqsanger.gz | |||
| SRR7663751_2.fastq.gz | Fastqsanger.gz | |||
| SRR7663752_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:We studied the effects of endogenous expression of the melanoma oncogene RAC1 P29S in BRAF V600E;PTEN hemizygous mouse melanomas.
2018-08-10 | GSE118344 | GEO
Project description:We studied the effects of long-term endogenous expression of the melanoma oncogene RAC1 P29S using melanocyte cultures isolated from transgenic mice
2018-08-10 | GSE118343 | GEO
Project description:Endogenous RAC1 P29S in mouse melanocytes
| PRJNA485293 | ENA
Project description:Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, with mutations of its upstream regulator, the RAC-GEF PREX2, also commonly detected. Crucially, RAC1 mutations are associated with resistance to BRAF-targeting therapies. Despite the role of its homologue PREX1 in melanomagenesis, and evidence that some truncating PREX2 mutations drive increased RAC1 activity, no hotspot mutations have been identified, and the impact of PREX2 mutation remains contentious. Here, we use genetically engineered mouse models and patient-derived BRAFV600E-driven melanoma cell lines to dissect the role of PREX2 in melanomagenesis and response to therapy. We show that while PREX2 is dispensable for the initiation and progression of melanoma, its loss confers sensitivity to clinically relevant therapeutics. Importantly, genetic and pharmacological targeting of the RAC1 effector kinase PI3Kβ phenocopies PREX2 loss, sensitizing our model systems to therapy. Our data reveal a druggable PREX2/RAC1/PI3Kβ signalling axis in BRAF-mutant melanoma that could be exploited clinically.
2024-11-22 | GSE281123 | GEO
Project description:RAC1P29S is the third most prevalent hotspot mutation in sun-exposed melanoma. RAC1 alterations in cancer are correlated with poor prognosis, resistance to standard chemotherapy, and insensitivity to targeted inhibitors. Although RAC1P29S mutations in melanoma and RAC1 alterations in several other cancers are increasingly evident, the RAC1-driven biological mechanisms contributing to tumorigenesis remain unclear. Lack of rigorous signaling analysis has prevented identification of alternative therapeutic targets for RAC1P29S-harboring melanomas. To investigate the RAC1P29S-driven effect on downstream molecular signaling pathways, we generated an inducible RAC1P29S expression melanocytic cell line and performed RNA-sequencing (RNA-seq) coupled with multiplexed kinase inhibitor beads and mass spectrometry (MIBs/MS) to establish enriched pathways from the genomic to proteomic level. Our proteogenomic analysis identified CDK9 as a potential new and specific target in RAC1P29S-mutant melanoma cells.In vitro, CDK9 inhibition impeded the proliferation of in RAC1P29S-mutant melanoma cells and increased surface expression of PD-L1 and MHC Class I proteins.In vivo, combining CDK9 inhibition with anti-PD-1 immune checkpoint blockade significantly inhibited tumor growthonly in melanomas that expressed the RAC1P29Smutation. Collectively, these results establish CDK9 as a novel target in RAC1-driven melanoma that can further sensitize the tumor to anti-PD-1 immunotherapy.
2024-06-12 | GSE248218 | GEO
Project description:We studied the effects of acute activation of the melanoma oncogene RAC1 P29S using a tamoxifen-inducible ER-fusion protein system in mouse melanocytes
2018-08-10 | GSE118349 | GEO
Project description:The therapeutic potential of neurotrophic factors has been hampered by their inability to achieve adequate tissue penetration. Brain blood vessels, however, could be an alternative target for neuro-salvage therapies by virtue of their close proximity to neurons. Here we show that hemizygous deletion of Rac1 in mouse endothelial cells (ECs) attenuates brain injury and edema following focal cerebral ischemia. To explore the mechanisms whereby decrease of Rac1 in ECs provide neuroprotection, ECs were derived from Rac1+/+ and Rac1+/- mice. Microarray analysis was performed to determine the differential gene expression between Rac1+/+ and Rac1+/- ECs. Rac1+/+ and Rac1+/- ECs were cultured to subconfluence. Total RNA was extracted and reverse transcribed. Rac1+/+ (n = 2) and Rac1+/- (n = 2) EC cDNAs were labeled with Cy3 and Cy5, respectively, and equimolar mixtures of labeled Rac1+/+ and Rac1+/- probes were hybridized to 2 slides (sample #21648, #21649). Additionally, Rac1+/+ (n = 2) and Rac1+/- (n=2) EC cDNAs labeled with Cy5 and Cy3 (dye-swapping) were hybridized to 2 slides (sample #21650, #21651). Comparison of signal intensities between Rac1+/+ (channel 2) and Rac1+/- (channel 1) was conducted on each slide (sample), and the ratio of intensities from 4 slides were statistically assessed for each gene feature to investigate differential gene expression.
2009-03-15 | E-GEOD-15003 | biostudies-arrayexpress
Project description:The microarray was conducted from RNA isolated from mouse mammary glands harvested from Involution day 2 mice. Cre-mediated specific Rac1 gene deletion in luminal mammary epithelial cells was achieved by crossing Rac1fx/fxRosaYFP mice with WAPiCreTg/⢠mice to produce Rac1fx/fxYFP ;WAPiCreTg/⢠(Rac1-/-) mice. Rac1fx/fxYFP mice that lacked the Cre gene were used as wild type (WT) controls. The RNA was isolated from the inguinal gland 4 for each mouse
2016-10-31 | E-MTAB-5019 | biostudies-arrayexpress
Project description:The therapeutic potential of neurotrophic factors has been hampered by their inability to achieve adequate tissue penetration. Brain blood vessels, however, could be an alternative target for neuro-salvage therapies by virtue of their close proximity to neurons. Here we show that hemizygous deletion of Rac1 in mouse endothelial cells (ECs) attenuates brain injury and edema following focal cerebral ischemia. To explore the mechanisms whereby decrease of Rac1 in ECs provide neuroprotection, ECs were derived from Rac1+/+ and Rac1+/- mice. Microarray analysis was performed to determine the differential gene expression between Rac1+/+ and Rac1+/- ECs.
2009-03-16 | GSE15003 | GEO
Project description:To study recombination at the fine-scale, we used high-throughput sequencing of 300 to 1,000 crossovers within the RAC1 R gene hotspot. This revealed focused intragenic crossovers, overlapping exons encoding the TIR, NBS and LRR domains. To examine the role of recombination pathways, we repeated this experiment in recq4a recq4b, fancm and recq4a recq4b fancm mutants. Finally, in order to investigate how varying patterns of interhomolog divergence influence local patterns of crossover frequency, we repeated RAC1 pollen typing sequencing in different F1 hybrids.
2018-07-01 | E-MTAB-6333 | biostudies-arrayexpress