Advanced ovarian cancers are initially responsive to chemotherapy with platinum drugs but develop drug resistance in most cases. We showed recently that hepatocyte growth factor (HGF) enhances death of human ovarian cancer cell lines treated with cisplatin (CDDP) and that this effect is mediated by the p38 mitogen-activated protein kinase. In this work, we integrated genome-wide expression profiling, in silico data survey, and functional assays to identify transcripts regulated in SK-OV-3 ovarian cancer cells made more responsive to CDDP by HGF. Using oligonucleotide microarrays, we found that HGF pretreatment changes the transcriptional response to CDDP. Quantitative reverse transcription-PCR not only validated all the 15 most differentially expressed genes but also confirmed that they were primarily modulated by the combined treatment with HGF and CDDP and reversed by suppressing p38 mitogen-activated protein kinase activity. Among the differentially expressed genes, we focused functional analysis on two regulatory subunits of the protein phosphatase 2A, which were down-modulated by HGF plus CDDP. Decrease of each subunit by RNA interference made ovarian cancer cells more responsive to CDDP, mimicking the effect of HGF. In conclusion, we show that HGF and CDDP modulate transcription in ovarian cancer cells and that this transcriptional response is involved in apoptosis regulation. We also provide the proof-of-concept that the identified genes might be targeted to either increase the efficacy of chemotherapeutics or revert chemotherapy resistance.
Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin.
Cell line
View SamplesSpecial AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor induced by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. In this study, we investigated the role of SATB1 in T helper cell differentiation by performing gene expression profiling of human differentiating Th cells in which expression of SATB1 was downregulated by RNA interference (RNAi). Our results indicate that SATB1 is involved in the regulation of more than three hundred genes in primary human CD4+ T cells, including several IL-12 and/or IL-4 regulated factors, suggesting a role in the development or function of Th subtypes.
SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
No sample metadata fields
View SamplesThe biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
No sample metadata fields
View SamplesThe aim of this study was to identify genes regulated by IL-12, IL-18 and IFN-alpha during early differentiation of human Th1 cells
Activating transcription factor 3 is a positive regulator of human IFNG gene expression.
Specimen part
View SamplesThe aim of the dataset was to study on genome-wide level the effect of PIM kinase (PIM1+PIM2+PIM3) knockdown in gene expression on early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) polarizing conditions.
Proviral integration site for Moloney murine leukemia virus (PIM) kinases promote human T helper 1 cell differentiation.
Specimen part
View SamplesWe found that hyperglycemia and elevated fatty acids in diabetes could activate protein kinase C- isoforms and selectively induce insulin resistance via inhibiting vascular insulin signaling.
Insulin decreases atherosclerosis by inducing endothelin receptor B expression.
Age, Specimen part, Disease, Disease stage, Treatment
View SamplesThe requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling using microarray technology.
Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
Sex, Specimen part, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Specimen part
View SamplesThe aim of this dataset was to study in detail the transcription kinetics initiated by cytokine IL-4 in early differentiation of Th2 cells.
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Specimen part
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