About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesWe sought to detect predictive markers related to a Src kinase inhibitor (saracatinib) sensitivity in ovarian cancer. Cell proliferation assays assigned 18 ovarian cancer cell lines to sensitive or resistant to this drug.
PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines.
Specimen part
View SamplesAnalysis of gene expression on day four and day six after tumor inoculation.
Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth.
Specimen part
View SamplesEleven NSCLC cell lines with widely divergent gefitinib sensitivities were compared using gene expression. Genes associated with gefitinib response were used to classify additional NSCLC lines with unknown gefitnib sensitivity.
Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines.
No sample metadata fields
View SamplesHLX was found as a VEGF-A induced gene in HUVEC (B.Schweighofer, submitted). In order to detect genes regulated by HLX HUVEC were infected by recombinant adenovirus expressing HLX for 4, 8, 16 and 32h. RNA was isolated and subjected to microarray analysis using Affymetrix microarray.
The VEGF-regulated transcription factor HLX controls the expression of guidance cues and negatively regulates sprouting of endothelial cells.
No sample metadata fields
View SamplesDespite initial and often dramatic responses of epidermal growth factor receptor (EGFR)-addicted lung tumors to the EGFR-specific tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, nearly all develop resistance and relapse. To explore novel mechanisms mediating acquired resistance, we employed non-small-cell lung cancer (NSCLC) cell lines bearing activating mutations in EGFR and rendered them resistant to EGFR-specific TKIs through chronic adaptation in tissue culture. In addition to previously observed resistance mechanisms including EGFR-T790M ''gate-keeper'' mutations and MET amplification, a subset of the seven chronically adapted NSCLC cell lines including HCC4006, HCC2279 and H1650 cells exhibited marked induction of fibroblast growth factor (FGF) 2 and FGF receptor 1 (FGFR1) mRNA and protein. Also, adaptation to EGFR-specific TKIs was accompanied by an epithelial to mesenchymal transition (EMT) as assessed by changes in CDH1, VIM, ZEB1 and ZEB2 expression and altered growth properties in Matrigel. In adapted cell lines exhibiting increased FGF2 and FGFR1 expression, measures of growth and signaling, but not EMT, were blocked by FGFR-specific TKIs, an FGF-ligand trap and FGFR1 silencing with RNAi. In parental HCC4006 cells, cell growth was strongly inhibited by gefitinib, although drug-resistant clones progress within 10 days. Combined treatment with gefitinib and AZD4547, an FGFR-specific TKI, prevented the outgrowth of drug-resistant clones. Thus, induction of FGF2 and FGFR1 following chronic adaptation to EGFR-specific TKIs provides a novel autocrine receptor tyrosine kinase-driven bypass pathway in a subset of lung cancer cell lines that are initially sensitive to EGFR-specific TKIs. The findings support FGFR-specific TKIs as potentially valuable additions to existing targeted therapeutic strategies with EGFR-specific TKIs to prevent or delay acquired resistance in EGFR-driven NSCLC. Overall design: Examination of mRNA levels in DMSO and gefitinib-resistant cultures of HCC4006 and HCC827. Each group has two replicates.
A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop.
Specimen part, Cell line, Treatment, Subject
View SamplesWe used microarrays to detail the global transcriptional response mediated by ERalpha or ERbeta to the phytoestrogen genistein in the MCF-7 human breast cancer cell model.
Estrogen Receptors alpha and beta as determinants of gene expression: influence of ligand, dose, and chromatin binding.
No sample metadata fields
View SamplesThe MCF-7 were infected with either control adenovirus expressing B-galactosidase (Ad) or adenovirus expressing ERB (AdERbeta) for 72 h. For knockdown of the endogenous ERa in MCF-7 cells, cells were treated with siRNA for 24h (AdERbeta+SiERalpha). Then cells were treated with Veh (0.1% EtOH), 10 nM E2 or 1 uM BEs (botanical extracts) for 24h. Overall design: Duplicate samples run; treatment after knockdown included a control treatment (V), estradiol (E2) or botanical extracts; genistein (Gen), S-equol, liquiritigenin (Liq)
Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens.
No sample metadata fields
View SamplesScope: Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here.
Isoflavones in soy flour diet have different effects on whole-genome expression patterns than purified isoflavone mix in human MCF-7 breast tumors in ovariectomized athymic nude mice.
Cell line
View SamplesDevelopment, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling. Overall design: Transgenic Drosophila melanogaster fruitflies carrying strong, ubiquitously expressed pre-miR277 hairpins (wt and two mutant versions) were dissected, total RNA was extracted from the abdomen and gel-purified for size selection (~18-30 nt). Digested plasmid samples were compared to those of circular plasmids and a nontransfected control. The purpose of this experiment was to demonstrate the extent of expression from mutant pre-miR277 hairpins, mut1 should abolish Drosha-processing while mut2 is conservative.
Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan.
Specimen part, Subject
View Samples