Deregulation of the transforming growth factor- (TGF) signaling pathway in epithelial ovarian cancer has been reported, but the precise mechanism underlying disrupted TGF signaling in the disease remains unclear. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate genome-wide screening of TGF-induced SMAD4 binding in epithelial ovarian cancer. Following TGF stimulation of the A2780 epithelial ovarian cancer cell line, we identified 2,362 SMAD4 binding loci and 318 differentially expressed SMAD4 target genes. Comprehensive examination of SMAD4-bound loci, revealed four distinct binding patterns: 1) Basal; 2) Shift; 3) Stimulated Only; 4) Unstimulated Only. SMAD4-bound loci were primarily classified as either Stimulated only (74%) or Shift (25%), indicating that TGF-stimulation alters SMAD4 binding patterns in epithelial ovarian cancer cells compared to normal epithelial cells. Furthermore, based on gene regulatory network analysis, we determined that the TGF-induced SMAD4-dependent regulatory network was strikingly different in ovarian cancer compared to normal cells. Importantly, the TGF/SMAD4 target genes identified in the A2780 epithelial ovarian cancer cell line were predictive of patient survival, based on in silico mining of publically available patient data bases. In conclusion, our data highlight the utility of next generation sequencing technology to identify genome-wide SMAD4 target genes in epithelial ovarian cancer. The results link aberrant TGF/SMAD signaling to ovarian tumorigenesis. Furthermore, the identified SMAD4 binding loci, combined with gene expression profiling and in silico data mining of patient cohorts, may provide a powerful approach to determine potential gene signatures with biological and future translational research in ovarian and other cancers.
ChIP-seq defined genome-wide map of TGFβ/SMAD4 targets: implications with clinical outcome of ovarian cancer.
Cell line, Treatment
View SamplesGene expression (by Affymetrix GeneChip Human 1.0ST) profiling of biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples) (GSE31826).
Decitabine reactivated pathways in platinum resistant ovarian cancer.
Age
View SamplesMouse model for Fetal Alcohol Syndrome. Embryos exposed to alcohol in controlled environment to assess teratogenic effects.
Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome.
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Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer.
Cell line
View SamplesCisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, we measured gene expression alterations associated with cisplatin resistance.
Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer.
Cell line
View SamplesFull title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells
MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways.
Cell line, Treatment
View SamplesCompare the expression pattern of 17b-estradiol responsive genes in parent, OHT-resistant and ICI-resistant breast cancer cells.
Diverse gene expression and DNA methylation profiles correlate with differential adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant.
No sample metadata fields
View SamplesMDA-MB-231 cells transfected with pcDNA-vector or pcDNA-LKB1 were analyzed for changes in gene expression. Results provide insight into genes regulated by LKB1 signaling with implications in tumor and metastasis suppression in breast cancer. Overall design: 4 samples, duplicates of -vector and -LKB1 stable cell lines
Regulation of triple-negative breast cancer cell metastasis by the tumor-suppressor liver kinase B1.
No sample metadata fields
View SamplesUnlike ovarian cancer, normal ovarian epithelium response to TGFb1 induced growth inhibition. This time course study tried to idenify genes that showed changes after additionof TGFb1 in immortalized ovarian surface epithelial cells (IOSE) which is derived from normal ovarian epithelial cells
An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification.
Specimen part
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