This SuperSeries is composed of the SubSeries listed below.
Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis.
Specimen part, Disease
View SamplesMelanoma is one of the most aggressive and treatment-resistant cancers. It represents the most life-threatening neoplasm of the skin, and its incidence has been increasing for the last three decades. Melanoma evolves from the local transformation of melanocytes to primary tumors, which can metastasize to multiple organs. Brain metastases represent one of the most significant causes of death in cutaneous melanoma patients. Despite aggressive multi-modality threapy, patients with melanoma brain metastasis have a median survival of less than a year, with a majority of these patients dying as a result of their intracranial disease. To identify alterations in gene expression related to brain metastasis, we used Affymetrix expression arrays to assess differentially expressed genes in melanocytes, lymph node metastases, and brain metastases.
Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis.
Specimen part, Disease
View SamplesConjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
No sample metadata fields
View SamplesOverexpression of fatty acid synthase (FAS) has been reported in both malignant and premalignant breast lesions, and has been associated with poor outcome. FAS has gained interest as a metabolic target for the treatment of breast cancer based on evidence that blockade with the antifungal antibiotic, cerulenin or synthetic inhibitor C75 inhibits proliferation of breast cancer cells and delays tumor development. Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit FAS in bovine mammary adipose. Based on previously well-documented anti-tumor activity of CLA, we hypothesized that one mechanism of CLAs anti-tumorigenic activity may be metabolic blockade of FAS. We fed virgin PyV-MT transgenic mice a diet supplemented with either 1% CLA, as mixed isomers, or control chow for four weeks. Tissue histology was determined by H&E staining. cDNA microarray and real-time quantitative PCR were performed to determine relative expression of lipogenic genes. Western blots were used to examine relative protein expression of FAS. Differences in protein densitometry were analyzed using Students 2-sided T-test. Probability was determined using the binomial sign test. Level of significance for all tests was 0.05. H&E staining revealed a shift towards advanced mammary lesions in the CLA-fed mice compared to control animals (24/26 vs. 11/26) (p for trend < 0.001). Microarray analysis revealed a >2-fold decrease in FAS in the CLA-fed group compared to controls, and was confirmed by quantitative RT-PCR (p < 0.001) and Western blot. The decrease in FAS mRNA expression was unexpectedly associated with more advanced disease (p for trend < 0.01). Conclusions: Dietary CLA suppressed fatty acid synthase in the mammary glands of the PyV-MT mouse while promoting mammary tumor progression.
No associated publication
Sex, Age, Specimen part
View SamplesWe treated melanoma cells with BRAF mutation with BRAF inhibitor and screened for BRAF inhibitor resistant cells. We extracted total mRNA from parental cells and resistant cell lines. We compared their expression by carried out Affymetrix Huex 1.0 ST expression array.
Epigenetic changes of EGFR have an important role in BRAF inhibitor-resistant cutaneous melanomas.
No sample metadata fields
View SamplesWe performed micrarrays to investigate neuronal gene expression changes during acute inflammatory CNS axon injury using the murine myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) model. The present study was assigned to assess the direct and indirect endogenous neuronal response to spinal axonal injury in the motor and sensory cortex.
Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation.
Sex, Specimen part, Treatment
View SamplesWe isolated mutants in Arabidopsis with enhanced ambient temperature response. Microarray analysis was performed to understand the extent to which ambient temperature transcriptome is perturbed in the mutants in comparison with the WT at non inductive 12 C and after shift to inductive 27 C for 2 h and 24 h.
H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis.
Specimen part
View SamplesDetermining the role of the Mediator subunit MED25/PFT1 in coordinating the expression of glucose responsive genes in Arabidopsis thaliana
No associated publication
Age, Specimen part, Time
View SamplesMany animal and plant species exhibit increased growth rates, reach larger sizes and, in the cases of crops and farm animals, produce higher yields when bred as hybrids between genetically differing strains, a phenomenon known as hybrid vigour or heterosis. Despite the importance of heterosis, and its extensive genetic analysis, there has been little understanding of its molecular basis. We aimed to determine whether characteristics of the leaf transcriptome, as an indicator of the innate functional genetic architecture of a plant line, could be used as markers to predict heterosis and the performance of hybrids, a methodology we term Association Transcriptomics. Relationships between transcript abundance of specific genes and the values of heterosis and heterosis-dependent traits were identified and mathematical models were constructed that relate gene expression characteristics in inbred lines of Arabidopsis thaliana and maize with vegetative biomass and for grain yield, respectively, in corresponding hybrids.
No associated publication
Specimen part
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