3D cultivation of cells lead to changes in morphology of the cells. This is likely to explain the higher radioresistance of cells growing in 3D compared to cells growing in 2D cell culture.
Genome-wide gene expression analysis in cancer cells reveals 3D growth to affect ECM and processes associated with cell adhesion but not DNA repair.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells.
Cell line
View SamplesThe function of cell-cell contact for radiochemosensitivity is unclear. Here, we investigate the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines.
Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells.
Cell line
View SamplesThree human ER+ breast cancer cell lines--MCF-7, T47-D, BT-474--grown with or without estradiol (E2).
GREB 1 is a critical regulator of hormone dependent breast cancer growth.
Cell line
View SamplesERa is essential for the anti-proliferative response of breast cancer cells not only to estrogen antagonists, but also to estrogen withdrawal by means of aromatase inhibitors. We explored here one of the simplest explanation for this, consisting in the possibility that ERa may have a wide genomic function in absence of ligands. The genomic binding of ERa in the complete absence of estrogen was then studied using hormone-dependent MCF7 cells, by chromatin immunoprecipitation sequencing. From these data, 4.2K highly significant binding events were identified, which were further confirmed by comparing binding events in cells expressing ERa to cells silenced for ERa. Apo-ERa binding sites were distributed close to genes with functions associated to cell growth and epithelial maintenance and show significant overlap with binding of other transcription factors important for luminal epithelial breast cancer. Interestingly, we found that upon ERa silencing cognate gene transcription in absence of estrogen is downregulated and this is accompanied by increased H27Kme3 at ERa binding sites. RNA-Seq experiments showed that unliganded ERa controls basal transcription widely, including both coding and noncoding transcripts. Genes affected by ERa silencing can be easily functionally related to mammary epithelium differentiation and maintenance, especially when considering downregulated genes. Additional functions related to inflammatory and immune response was observed. Our data unravel unexpected actions of ERa in breast cancer cells and provide a novel framework to understand success and failure of hormone therapy in breast cancer. Overall design: Examination of unligandend estrogen receptor alpha (aERa) DNA interactions in control and aERa siRNA treated MCF7 cells.
Dissecting the genomic activity of a transcriptional regulator by the integrative analysis of omics data.
No sample metadata fields
View SamplesPublic transcriptomics studies have shown that several genes display pronounced gender differences in their expression in the human brain, and these differences may influence the clinical manifestations and risk for neuronal disorders. While disease relevant implications have already been proposed for gender differences in hormone levels, life style and genetic diversity, a systems level analysis of brain gene expression disparities between the genders in the context of brain disorders like Alzheimers disease (AD) has not yet been conducted.
Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies.
Specimen part, Treatment
View SamplesGene expression profiles of paired normal adjacent mucosa and tumor samples from 98 individuals and 50 healthy colon mucosae, were obtained through Affymetrix Human Genome U219 Arrays. This dataset is in the context of the COLONOMICS project and to query additional information you can visit the project website www.colonomics.org.
Discovery and validation of new potential biomarkers for early detection of colon cancer.
Sex, Age, Disease, Subject
View SamplesDiffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, resulting in the death of 200-300 children each year in the United States. Recently it was discovered that approximately 25% of all DIPG cases harbor activating mutations in ACVR1, a gene that encodes Activin A receptor (ALK2), a receptor in the bone morphogenetic protein (BMP) pathway, and that DIPGs with ALK2 mutations commonly harbor an H3.1K27M mutation. Herein, we used the RCAS/TVA retroviral system to study the effects of ACVR1 mutations and H3.1K27M on DIPG pathogenesis. In vitro expression of R206H ACVR1 with and without H3.1K27M in nestin-expressing brainstem progenitors resulted in upregulation of mesenchymal markers and gene set enrichment analysis (GSEA) revealed Stat3 pathway activation. Neonatal expression of ACVR1 R206H or G328V in combination with H3.1K27M and p53 deletion in nestin-expressing brainstem progenitors induced glioma-like lesions expressing mesenchymal markers with Stat3 activation but was not sufficient for full gliomagenesis. In combination with platelet-derived growth factor A (PDGFA) signaling, ACVR1 R206H and H3.1K27M significantly decreased survival and increased tumor incidence. We demonstrate that targeting the BMP signaling pathway may be an effective therapeutic strategy to treat ACVR1 R206H mutant DIPGs. Exogenous Noggin expression at tumor initiation significantly increased tumor latency and treatment of ACVR1 R206H mutant murine DIPGs with LDN212854, an ACVR1 inhibitor, significantly prolonged their survival. We confirm relevance of our model to the human disease as human DIPG models with ACVR1 mutations were also sensitive to treatment with LDN212854 in vitro. Altogether, our studies demonstrate that ACVR1 R206H and H3.1K27M promote tumor initiation, accelerate gliomagenesis, promote a mesenchymal profile in part due to Stat3 activation, and identify LDN212854 as a promising compound to treat children with DIPG. Overall design: We use RNAseq to study the transcriptomal effects of ACVR1 WT or R206H ACVR1 mutation alone and in combination with H3.1K27M mutation on murine nestin-expressing brainstem progenitors at P3-5 (using RCAS/TVA). Key findings were validated by Real-Time PCR.
ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis.
Specimen part, Subject
View SamplesThe highly conserved Wnt signaling pathway drives intestinal homeostasis across species. Apc is a negative regulator of Wnt signaling. Loss of function mutations in Apc are found in 80-90% of human colorectal cancers. Importantly, Apc loss is widely known as the key driving event in the disease.
Intestinal stem cell overproliferation resulting from inactivation of the APC tumor suppressor requires the transcription cofactors Earthbound and Erect wing.
Sex, Age, Specimen part
View SamplesCryopreservation consists of preserving living cells or tissues at <-100C and has many applications in, for instance, stem cell and organ banking. Cryoprotectant agents, like ethylene glycol, are required for successful cryopreservation but have toxic side effects due to largely unknown mechanisms. In this work, we studied the toxicity of ethylene glycol in Human Umbilical Vein Endothelial Cells (HUVECs). Exposing cells to 60% ethylene glycol for two hours at 4C resulted in a slight decrease in cell growth, suggesting a modest toxicity of ethylene glycol and that HUVECs do not exhibit particular sensitivity to it. Gene expression analysis with whole genome micro-arrays revealed signatures indicative of a generalized stress response at 24 hours after stress and recovery at 72 hours, involving signaling pathways, glycoproteins, and genes involved in extracellular and transmembrane functions. These results reveal a new paradigm and signatures for future experiments in elucidating the toxicity effects of ethylene glycol in vascular endothelial cells.
Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol.
Specimen part, Treatment
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