Renal cell carcinoma (RCC) is among the ten most common malignancies. By far, the most common histology is clear cell (ccRCC). The Cancer Genome Atlas and other large scale sequencing studies of ccRCC have been integral to the current understanding of molecular events underlying RCC and its biology. However, these data sets have focused on primary RCC which often demonstrates indolent behavior. In contrast, metastatic disease is the major cause of mortality associated with ccRCC. However, data sets examining metastatic tumor are sparse. We therefore undertook an integrative analysis of gene expression and DNA methylome profiling of metastatic ccRCC in addition to primary RCC and normal kidney. Integrative analysis of the methylome and transcriptome identified over 30 RCC specific genes whose mRNA expression inversely correlated with promoter methylation including several known targets of hypoxia inducible factors (HIFs). Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation. Collectively, our data provide novel insight into biology of aggressive RCC. Furthermore, they demonstrate a clear role for epigenetics in the promotion of HIF signaling and invasive phenotypes in renal cancer.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesUnderstanding gene expression changes during transformation from normal tissue to primary RCC and then to metastasis is important. Such analysis is pivotal for undertanding biology in renal cancer and also to unearth novel gene targets.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesGene expression were identified with or without CD24 gene silencing in Du145 cells.
Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation.
Sex, Specimen part, Cell line
View SamplesTranscription profiling by array of mouse male retinas to investigate IGF-I-induced chronic gliosis and retinal stress
Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy.
Sex, Specimen part
View SamplesIGF-I exert multiple effects in different retinal cell populations in both physiological and pathological conditions. Transgenic mice overexpressing IGF-I in the retina showed impaired electroretinographic responses at 6-7 months of age that worsen with age. This retinal neuronal dysfunction was correlated with the loss of rod photoreceptors, bipolar, ganglion and amacrines cells. Neuronal alterations were preceded by the overexpression of retinal stress markers, acute phase proteins and gliosis-related genes. IGF-I overexpression leads to chronic gliosis and microgliosis in TgIGF-I retinas, with mild oxidative stress, impaired recycling of glutamate and defective potassium buffering. These impaired supportive functions can contribute to neurodegeneration in TgIGF-I retinas, together with the increased production of pro-inflammatory cytokines, potential mediators of neuronal death.
Insulin-like Growth Factor 2 Overexpression Induces β-Cell Dysfunction and Increases Beta-cell Susceptibility to Damage.
Sex, Specimen part
View SamplesMany concurrent arrays were run for different projects. All test conditions were tested in all animal models. Animal models were (i) healthy CD1 mice (abbreviation CN), or (ii) STZ-induced diabetic CD1 littermates (STZ). Treatment conditions were (i) untreated animals (no prefix), (ii) treatment with 30ul saline and electrotransfer ("e" prefix), (iii) treatment with 75ug noncoding parental plasmid pGG2-CMV ("p" prefix), or (iv) treatment with 37.5ug each (75ug net) of pGG2-CMV-hIns and pGG2-CMV-rGck expressing human insulin and rat glucokinase respectively ("t" prefix). All samples were harvested 7 days after treatment.
No associated publication
Sex, Age, Specimen part, Disease, Disease stage, Subject, Compound, Time
View Samples