Complex three-dimensional (3D) in vitro model systems that recapitulate human tumor biology are essential to better understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellula communication, nutrient and oxygen gradients, and cell polarity that is lacking in traditional two-dimensional (2D) monolayer cultures. In the present study, we could demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of Erb family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we could provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.
Organotypic three-dimensional cancer cell cultures mirror drug responses <i>in vivo</i>: lessons learned from the inhibition of EGFR signaling.
Cell line
View SamplesWe used microarrays to compare the global programme of gene expression in HTLV-positive, ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells.
Elevated cyclic AMP levels in T lymphocytes transformed by human T-cell lymphotropic virus type 1.
Specimen part
View SamplesThe Tesi system allows analysis of HTLV-1 Tax's impact on the transcriptome of a human CD4+ T-cell which is not derived from leukemia but directly from normal human lymphocytes. By comparing cells with and without Tax, one can specifically filter for celluar genes that are either activated or repressed in the presence of Tax.
Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1-infected cultured and patients' T cells by the viral Tax oncoprotein.
No sample metadata fields
View SamplesGenome-wide transcriptome analyses have allowed for systems- level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein complex stoichiometry are lagging behind. Here, we employ deep sequencing and iTRAQ technology to determine transcript and protein expression changes of a Drosophila brain tumour model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analysing the co-regulation of potential subunits. Our comprehensive transcriptome and proteome data provide a rich resource for quantitative biology and offer novel insights into understanding post- transcriptional gene regulation in a tumour model. Overall design: Transcriptomes of 1-3 day old adult female Drosophila melanogaster heads of control and brat mutant were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation.
Subject
View Samplesdetermination of gene regulation by sterol and sphingolipid composition
Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.
Sex
View SamplesBackground: MicroRNA-196b-5p (miR-196b-5p) has been previously involved in carcinogenesis, though its role in colorectal cancer (CRC) patients and biology remains controversially. In our current study, we systematically explored the clinical significance and biological relevance of miR-196b-5p, as well as the underlying molecular mechanisms regulated by miR-196b-5p in colorectal cancer.
miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.
Cell line
View SamplesThe goal of the study was to compare transcriptome changes in HeLa cells after infection with recombinant Thogoto virus (wild-type, ML deletioin mutant or ML SW mutant not able to interact wiith TFIIB. While wild-type virus is able to inhibit inflammatory genes, ML deletion mutant and TFIIB-non-interacting mutant lose this effect on gene transcription. Overall design: Examination of transcriptome changes in HeLa cells under steady state or after THOV infection using Illumina HiSeq.
Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer.
Cell line, Treatment
View SamplesKnockdown of H19 leads to cell cycle arrest, reduced cell proliferation, and reduced cell migration in HCT116 cells.
H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer.
Cell line, Treatment
View SamplesWe used microarrays to detail the global programme of gene expression following CTNNB1 knockdown in HCT116 cells
H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer.
Cell line, Treatment
View Samples