Adenovirus infection leads to increased glycolytic metabolism in host cells. Expression of a single gene product encoded within the E4 early transcription region, E4ORF1, is sufficient to promote increased glycolytic flux in cultured epithelial cells.
Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.
Cell lineView Samples
Affymetrix HG_U133 array sets (A and B chips) were used to determine the whole genome transcription profile of clinically documented and neuropathologically confirmed cases of sporadic Parkinson's disease as well as controls.
Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.
No sample metadata fieldsView Samples
Panel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines
Interleukin 32 expression in human melanoma.
Disease, Disease stage, Cell line, SubjectView Samples
The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
Doxycycline alters metabolism and proliferation of human cell lines.
Specimen part, Cell line, TreatmentView Samples
Alteration of the PTEN/PI3K pathway is associated with late stage and castrate resistant prostate cancer (CRPC). However, how PTEN loss involves in CRPC development is not clear. Here we show that castration-resistant growth is an intrinsic property of Pten-null prostate cancer (CaP) cells, independent of cancer development stage.PTEN loss suppresses androgen-responsive gene expressions by modulating androgen receptor (AR) transcription factor activity. Conditional deletion of AR in the epithelium promotes the proliferation of Pten-null cancer cells, at least in part, by down-regulating androgen-responsive gene FKBP5 and preventing PHLPP-mediated AKT inhibition. Our findings identify PI3K and AR pathway crosstalk as a mechanism of CRPC development, with potentially important implications for CaP etiology and therapy
Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth.
Specimen part, TimeView Samples
Microarray studies revealed that as a first hit, SV40 T/t-antigen causes deregulation of 462 genes in mammary gland cells (ME-cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell-proliferation specific and Rb-E2F dependent, causing ME-cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells, a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture, breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal-ME-cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal-ME-cells. The profile of retransformants shows that only 38 deregulated genes appear to be tumor-relevant and that none of them is considered to be a typical breast cancer gene.
Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.
No sample metadata fieldsView Samples
The first clinical trial testing the combination of targeted therapy with a BRAF inhibitor vemurafenib and immunotherapy with a CTLA-4 antibody ipilimumab was terminated early due to significant liver toxicities, possibly due to paradoxical activation of the MAPK pathway by BRAF inhibitors in tumors with wild type BRAF. MEK inhibitors can potentiate the MAPK inhibition in tumor, while potentially alleviating the unwanted paradoxical MAPK activation. With a mouse model of syngeneic BRAFV600E driven melanoma (SM1), we tested whether the addition of the MEK inhibitor trametinib would enhance the immunosensitization effects of the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression. Bioluminescent imaging and tumor infiltrating lymphocyte (TIL) phenotyping showed increased effector infiltration to tumors with dabrafenib, trametinib or dabrafenib plus trametinib with pmel-1 ACT combination. Intracellular IFN gamma staining of the TILs and in vivo cytotoxicity studies showed trametinib was not detrimental to the effector functions in vivo. Dabrafenib increased tumor associated macrophages and T regulatory cells (Tregs) in the tumors, which can be overcome by addition of trametinib. Microarray analysis revealed increased melanoma antigen, MHC expression, and global immune-related gene upregulation with the triple combination therapy. Given the up-regulation of PD-L1 seen with dabrafenib and/or trametinib combined with antigen specific ACT, we tested the triple combination of dabrafenib, trametinib with anti-PD1 therapy, and observed superior anti-tumor effect to SM1 tumors. Our findings support the testing of these combinations in patients with BRAFV600E mutant metastatic melanoma.
Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma.
Specimen part, Treatment, CompoundView Samples
Determing the influence of lipid metabolism on murine T cell blastogenesis. Gene expression studies from purified spleen and lymph node T cells with conditional deletion of the SREBP Cleavage Activating Protein (SCAP) ex vivo or activated with plate-bound anti-CD3 and CD28 antibodies for 6 h.
Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity.
Sex, Specimen partView Samples
This SuperSeries is composed of the SubSeries listed below.
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Specimen part, TreatmentView Samples