Identification of BCL2A1 as a stress-inducible gene in enhancing ovarian cancer cell survival in hypoxic condition
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: David Chan
PROVIDER: E-MTAB-9730 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Ovarian cancer cells treated with CDDP showed up-regulation of IRF-1 and IRF-7. The expression of putative IRF-1 target genes was modulated. CDDP triggered nuclear translocation of IRF-1 and IRF-1 silencing re-orchestrated the expression profiles of CDDP treated cells. Using microarrays, we evaluated the expression profiles of IRF-1 silenced SK-OV-3.
2013-12-31 | E-GEOD-38551 | biostudies-arrayexpress
Project description:This 58 arrays are the basis of our hypoxia story published in PLoS Medicine. The cell type, oxygen tension and time points are indicated. Abstract: BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Using regression correlation
2006-02-24 | E-GEOD-4185 | biostudies-arrayexpress
Project description:HGF sensitizes ovarian cancer cells to chemotherapeutics, e.g. cisplatin (CDDP), through a signaling cascade activated by its MET oncogene encoded receptor and transduced by the p38MAPK. This cascade results in the regulation of a common set of transcripts in three ovarian cancer cell lines, with different genetic profiles and susceptibility to drugs. In order to elucidate the mechanism of HGF dependent cell sensitization to drugs, the transcriptional response of the three ovarian cancer cell lines to HGF and CDDP were studied by microarray based transcription profiling
2013-12-31 | E-GEOD-24589 | biostudies-arrayexpress
Project description:All mammalian cells need oxygen. Inadequate oxygen (hypoxia) triggers cellular responses for survival and the maintenance of homeostasis. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1a protein. Despite the ubiquity and importance of hypoxia responses, very little is known about the variation in the global transcriptional response to hypoxia among different cell types and its links to tissue and cell-specific diseases. We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells (RPTECs), breast epithelial cells, smooth muscle (SMs), and endothelial cells (ECs) with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This exaggerated response was associated with a uniquely high level of HIF-1a RNA in renal cells and could be diminished by reducing HIF-1a expression via RNA interference (RNAi). A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in both breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Using regression correlation
2010-07-01 | E-GEOD-3537 | biostudies-arrayexpress
Project description:The high rates of mortality associated with epithelial ovarian cancer (EOC) are a direct consequence of its metastatic nature. Metastasis is dependent on many factors, among which activation of angiogenesis is most significant. Angiogenesis is, in turn, contingent upon the cellular response to hypoxia within the tumor microenvironment. Hypoxia-inducible factor 1 (HIF1) is a transcription factor composed of HIF1alpha and HIF1beta subunits and is the master regulator of the hypoxic response. It is therefore a critical mediator of tumor angiogenesis and metastasis. Regulation of HIF1 is primarily at the level of protein. In normoxia, the HIF1alpha subunit is hydroxylated via an oxygen- and iron-dependent mechanism and targeted for destruction. In hypoxia, low oxygen levels preclude hydroxylation and HIF1alpha is stabilized, allowing for its association with constitutively expressed HIF1beta to form bioactive HIF1. We have identified a novel mechanism of HIF1alpha regulation in EOC cells that involves microRNAs (miRs), ~22 nucleotide, non-coding RNA molecules that repress translation of target mRNAs by binding their 3’ untranslated regions (UTRs). Using microarray and qPCR analysis, we found that levels of miR-199a-1, a miR that is predicted in silico to target the HIF1alpha 3’ UTR, were reduced under hypoxia in EOC cells. We further demonstrated that miR-199a-1 directly targets the HIF1alpha 3’ UTR and overexpression of miR-199a-1 suppresses HIF1alpha protein levels and HIF1-driven gene expression. Moreover, cells stably overexpressing miR-199a-1 exhibit marked defects in migratory ability. These data were corroborated by our in vivo findings, which demonstrated that overexpression of miR-199a-1 causes significant reductions in tumor vessel density and tumor burden in nude mice. These findings provide insight into non-canonical, miR- and iron-based mechanisms of HIF1 regulation that may have important implications in the progression of EOC. miRNA expression analysis of A2780 epithelial ovarian cancer cells by microarrays
2011-09-23 | E-GEOD-32313 | biostudies-arrayexpress
Project description:OBJECTIVES: Amplification of the 11q13 locus is commonly observed in a number of human cancers including both breast and ovarian cancer. Cyclin D1 and EMS1 have been implicated as candidate oncogenes involved in the emergence of amplification at this locus. Detailed analysis of the 11q13 amplicon in breast cancer led to the discovery of four regions of amplification suggesting the involvement of other genes. Here, we investigate the role of EMSY, a recently described BRCA2 interacting protein, as a key element of the 11q13 amplicon in ovarian cancer. EMSY maps to 11q13.5 and is amplified in 13% of breast and 17% of ovarian carcinomas. METHODS: EMSY amplification was assessed by fluorescent in-situ hybridization (FISH) in 674 ovarian cancers in a tissue microarray and correlated with histopathological subtype and tumor grade. A detailed map of the 11q13 amplicon in 51 cases of ovarian cancer was obtained using cDNA-array-based comparative genomic hybridization (aCGH). To further characterize the role of EMSY within this amplicon, we evaluated both the amplification profiles and RNA expression levels of EMSY and two other genes from the 11q13 amplicon in an additional series of 22 ovarian carcinomas. : EMSY amplification was seen in 52/285 (18%) high grade papillary serous carcinomas, 4/27 (15%) high grade endometrioid carcinomas, 3/38 (8%) clear cell carcinomas, and 3/10 (30%) undifferentiated carcinomas. aCGH mapping of 11q13 in ovarian cancer showed that EMSY localized to the region with the highest frequency of copy number gain. Cyclin D1 and EMS1 showed a lower frequency of copy number gain. A highly significant correlation between EMSY gene amplification and RNA expression was also observed (P = 0.0001). This was a stronger correlation than for other genes at 11q13 including Cyclin D1 and PAK1. CONCLUSIONS: These findings support the role of EMSY as a key oncogene within the 11q13 amplicon in ovarian cancer. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Using regression correlation
2010-06-25 | E-GEOD-16408 | biostudies-arrayexpress
Project description:Knocking down of CSE1L made ovarian cancer cells, but not other cancer and normal cell lines, sensitized to cisplatin and triggered apoptosis. The nuclear localization in ovarian cancer cells suggested that CSE1L might primarily regulate transcription. . Using microarrays, we evaluated the expression profiles of CSE1L silenced SK-OV-3 and TOV-21G cells
2013-12-31 | E-GEOD-24429 | biostudies-arrayexpress
Project description:The transcriptional response to CDDP of three ovarian cancer cell lines was studied. These lines show different genetic profiles and display different susceptibilities to CDDP. The time and doses that resulted in the apoptotic death of each cell line was identified and used to study the expression profiles associated to CDDP-induced cell death in each cell line. CDDP: cis-diamminedichloroplatinum(II) In order to elucidate the mechanism of CDDP dependent cell susceptibilities to drugs, the transcriptional response of the three ovarian cancer cell lines to CDDP were studied by microarray based transcription profiling
2013-12-31 | E-GEOD-38545 | biostudies-arrayexpress
Project description:<h4>Background</h4>Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues.<h4>Results</h4>Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations.<h4>Conclusions</h4>The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to be considered in the design and early testing of such treatments.
2021-11-05 | MTBLS150 | MetaboLights
Project description:Purpose: To study differential mRNA and precursor miRNA expression under hypoxia exposure in cancer cells. We treated ovarian cancer cell line A2780 under hypoxia condition at different time points. Normoxi acultured cells at corresponding time point were used as controls.
2016-10-20 | GSE52695 | GEO