This SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Disease, Disease stage
View SamplesFrozen tissue specimens from primary breast tumors were collected and profiled using Affymetrix U133 plus 2 expression microarrays.
Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells.
Specimen part, Disease, Disease stage
View SamplesFrozen tissue specimens from primary breast tumors were collected under approved protocols and profiled using Affymetrix U133 series expression microarrays. This cohort was assembled at the National University Hospital (NUH), Singapore in 2003, and profiled at the Genome Institute of Singapore, Microarray and Expression Genomics Lab. Dr. Lance D. Miller (Wake Forest University School of medicine) directed the profiling work.
No associated publication
Specimen part, Disease, Disease stage
View SamplesFrozen tissue specimens from primary breast tumors were collected under IRB-approved protocols from 2 medical centers and profiled using Affymetrix U133 series expression microarrays. This cohort comprises of two subcohorts derived from the Institute Jules Bordet (IJB), Brussels (n=41) (2002) and Guys Hospital, London (n=7) (2003). Dr. Christos Sotiriou (Institute Jules Bordet) directed the microarray work in Brussels.
No associated publication
Specimen part, Disease, Disease stage
View SamplesOverexpression of a caspase-resistant form of Bcl-2 (D34A) in human umbilical vein endothelial cells (EC) implanted into immunodeficient mice promotes the maturation of human EC-lined microvessels invested by vascular smooth muscle cells (VSMC) of mouse origin. In contrast, EC implants not overexpressing Bcl-2 form only simple, uncoated EC tubes. Here we compare the phenotypes of vessels formed in vivo and the transcriptomes in vitro of EC expressing different forms of Bcl-2. Wild type Bcl-2, like the caspase resistant D34A Bcl-2 mutant, is anti-apoptotic in vitro and promotes VSMC recruitment in vivo, whereas a G145E mutant that has diminished anti-apoptotic activity in vitro does not promote vessel maturation in vivo. The D34A and wild type forms of Bcl-2, but not the G145E mutant form of Bcl-2 significantly regulate RNA transcripts previously associated with EC-VSMC interactions and VSMC biology, including matrix Gla protein, insulin like growth factor binding protein (IGFBP)-2, matrix metaloproteinase-14 (MMP14), ADAM17 and Stanniocalcin-1. These effects of Bcl-2 on the transcriptome are detected in EC cultured as angiogenic 3-D tubes but are attenuated in EC cultured as 2-D monolayers. Bcl-2-regulated transcription in EC may contribute to vascular maturation, and support design of tissue engineering strategies using EC.
Antiapoptotic activities of bcl-2 correlate with vascular maturation and transcriptional modulation of human endothelial cells.
No sample metadata fields
View SamplesZinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of human ADPGK, which encodes an ADP-dependent glucokinase (ADPGK), in tumour cell lines. The hypothesis tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two tumour cell lines (H460 and HCT116). All four lines had frameshift mutations in all alleles at the target site in exon 1 of ADPGK, and were ADPGK-null by immunoblotting. ADPGK knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 213% for the parental line to 6.40.8% (p=0.002) and 4.30.8% (p=0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when ADPGK was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of ADPGK in HCT116 cells caused few changes in global gene expression, knockout of ADPGK in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no effect on glycolysis as measured by glucose consumption or lactate formation under oxic or anoxic conditions, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the ADPGK knockouts, in some cases markedly so. Collectively, the results demonstrate that ADPGK can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of ADPGK is cell line dependent and appears to be unrelated to priming of glycolysis.
Expression and role in glycolysis of human ADP-dependent glucokinase.
Cell line
View SamplesIn addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid -oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated -oxidation-fueled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homolog of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses.
Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production.
Specimen part, Treatment
View SamplesAffymetrix microarray data was generated from MCF7 breast cancer cells treated in vitro with siRNAs against 78 transcription factors and signalling molecules.
Cell cycle gene networks are associated with melanoma prognosis.
Cell line
View SamplesOlive oil is correlated to long life and low rates of cancers and cardiovascular disease. The health benefits of the oil is contributed to the polyphenols. The polyphenols in olive leaf are simialr bit in high concentrations. We wanted to uncover whether measurable changes would occur with supplementation in human participants.
No associated publication
No sample metadata fields
View SamplesAffymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signalling molecules.
Cell cycle gene networks are associated with melanoma prognosis.
Cell line
View Samples