LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's disease.
Sex
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C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis.
Specimen part, Subject
View SamplesThe rediscovery of estrogen receptor (ESR1) mutations in metastatic breast cancer is current clinical scenario. We have modeled the three most frequent ESR1 mutations using stable lentiviral vectors in human breast cancer cell lines, and determined that they confer relative resistance to tamoxifen (Tam) in a cell-type specific manner due to distinct epigenetic changes. Resistance was only observed with concomitant engagement and activation of the insulin growth factor signaling pathway (IGF1R). The ESR1 mutants also exhibited enhanced binding with insulin growth factor receptor beta (IGF1R). The selective estrogen degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while the combination treatment with the mTOR inhibitor everolimus, restored Tam sensitivity. Since we detected relatively high frequencies of these three mutations in primary breast tumors, our results suggest that clinical targeted sequencing of both primary and metastatic tumors may be justified and comination therapies considered.
ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.
Cell line, Treatment
View SamplesObjective: An intronic GGGGCC-repeat expansion of C9ORF72 is the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The mechanism of neurodegeneration is unknown, but a direct effect on RNA processing mediated by RNA foci transcribed from the repeat sequence has been proposed.
C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis.
Specimen part, Subject
View SamplesAstrocyte dysfunction impacts their normal function, including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology.
Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype.
Specimen part
View SamplesRNA sequencing in NIH-3T3 cells Overall design: Transcriptome analysis for three biological replicates of pLX307, SOS1 WT, SOS1 N233Y, and KRAS G12V cells
Identification and Characterization of Oncogenic <i>SOS1</i> Mutations in Lung Adenocarcinoma.
Cell line, Subject
View SamplesHuman peripheral blood mononuclear cells were cultured in presence of H37Ra strain at 37oC, 5%CO2. Cellular aggregates were collected at 24h, and RNA extracted and hybridized to Affymetrix microarrays (HG-U133). Raw data from microarray experiments was analyzed with dCHIP and SAM programs to determine the significance of changes at the biological context.
Microarray analysis of the in vitro granulomatous response to Mycobacterium tuberculosis H37Ra.
Specimen part
View Sampleswe analyzed the gene expression profiles of Mat-Lylu cell lines (in duplicate) compared to G cell lines (in duplicate) using Affymetrix tools and dChip software. The objective was to find metastasis-associated genes in prostate cancer, using this in vitro model.
DNA microarray analysis reveals metastasis-associated genes in rat prostate cancer cell lines.
No sample metadata fields
View SamplesC2C12 cells are mouse skeletal muscle cells. These cells were transfected with shRNA against FoxO1, FoxO3, and FoxO4. FoxO1, FoxO3, and FoxO4 are the known paralogues expressed in this cell line.
Codependent activators direct myoblast-specific MyoD transcription.
No sample metadata fields
View SamplesTime and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
No sample metadata fields
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