Fdfaca3b-5315-4663-a725-01190a530ada - samples
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ABSTRACT:
PROVIDER: EGAD00001008144 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:SNP data of 28 sites required for the Ovarian cancer PRS (controls)
| EGAD00001008145 | EGA
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-02-23 | PXD004435 | Pride
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-03-30 | MSV000080810 | MassIVE
Project description:The genomic loci with copy number alterations are known to harbor cancer genes. We investigated a comprehensive panel of gastric cancer cell lines for their genome-wide copy number alterations. Eighteen gastric cancer cell lines were profiled using Affymetrix 500K SNP arrays. For copy number calculation, seven independent normal blood samples were profiled together. The copy numbers were calculated genome-wide, in these cell lines with high resolution and reveal the cell line specific amplification and copy number changes.
2015-08-04 | GSE51074 | GEO
Project description:The progesterone receptor (PR) and its coactivators are direct targets of activated cyclin-dependent kinases (CDKs) in response to peptide growth factors, progesterone, and deregulation of cell cycle inhibitors. Herein, using the T47D breast cancer model, we probed mechanisms of cell cycle-dependent PR action. In the absence of exogenous progestin, the PR is specifically phosphorylated during the G2/M phase. Accordingly, numerous PR target genes are cell cycle regulated, including HSPB8, a heat-shock protein whose high expression is associated with tamoxifen resistance. Progestin-induced HSPB8 expression required cyclin D1 and was insensitive to antiestrogens but blocked by antiprogestins or inhibition of specificity factor 1 (SP1). HSPB8 expression increased with or without ligand when cells were G2/M synchronized or contained high levels of cyclin D1. Knockdown of PRs abrogated ligand-independent HSPB8 expression in synchronized cells. Notably, PRs and cyclin D1 copurified in whole-cell lysates of transiently transfected COS-1 cells and in PR-positive T47D breast cancer cells expressing endogenous cyclin D1. PRs, cyclin D1, and SP1 were recruited to the HSPB8 promoter in progestin-treated T47D breast cancer cells. Mutation of PR Ser345 to Ala (S345A) or inhibition of CDK2 activity using roscovitine disrupted PR/cyclin D1 interactions with DNA and blocked HSPB8 mRNA expression. Interaction of phosphorylated PRs with SP1 and cyclin D1 provides a mechanism for targeting transcriptionally active PRs to selected gene promoters relevant to breast cancer progression. Understanding the functional linkage between PRs and cell cycle regulatory proteins will provide keys to targeting novel PR/cyclin D1 cross talk in both hormone-responsive disease and HSPB8-high refractory disease with high HSPB8 expression.
2014-02-27 | GSE46715 | GEO
Project description:Background Estrogen and progesterone are potent breast mitogens. In addition to steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and progesterone receptor (PR) actions via posttranslational events. Protein kinases commonly activated in breast cancers phosphorylate steroid hormone receptors (SRs) and profoundly impact their activities. Methods To better understand the role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs in 209 human breast tumors represented on 2754 individual tissue spots within a tissue microarray and assayed the regulation of this site in human tumor explants cultured ex vivo. To complement this analysis, we assayed PR target gene regulation in T47D luminal breast cancer models following treatment with progestin (promegestone; R5020) and antiprogestins (mifepristone, onapristone, or aglepristone) in conditions under which the receptor is regulated by Lys388 SUMOylation (K388 intact) or is SUMO-deficient (via K388R mutation to mimic persistent Ser294 phosphorylation). Selected phospho-PR-driven target genes were validated by qRT-PCR and following RUNX2 shRNA knockdown in breast cancer cell lines. Primary and secondary mammosphere assays were performed to implicate phospho-Ser294 PRs, epidermal growth factor signaling, and RUNX2 in breast cancer stem cell biology. Results Phospho-Ser294 PR species were abundant in a majority (54%) of luminal breast tumors, and PR promoter selectivity was exquisitely sensitive to posttranslational modifications. Phospho-PR expression and target gene programs were significantly associated with invasive lobular carcinoma (ILC). Consistent with our finding that activated phospho-PRs undergo rapid ligand-dependent turnover, unique phospho-PR gene signatures were most prevalent in breast tumors clinically designated as PR-low to PR-null (luminal B) and included gene sets associated with cancer stem cell biology (HER2, PAX2, AHR, AR, RUNX). Validation studies demonstrated a requirement for RUNX2 in the regulation of selected phospho-PR target genes (SLC37A2). In vitro mammosphere formation assays support a role for phospho-Ser294-PRs via growth factor (EGF) signaling as well as RUNX2 as potent drivers of breast cancer stem cell fate. Conclusions We conclude that PR Ser294 phosphorylation is a common event in breast cancer progression that is required to maintain breast cancer stem cell fate, in part via cooperation with growth factor-initiated signaling pathways and key phospho-PR target genes including SLC37A2 and RUNX2. Clinical measurement of phosphorylated PRs should be considered a useful marker of breast tumor stem cell potential. Alternatively, unique phospho-PR target gene sets may provide useful tools with which to identify patients likely to respond to selective PR modulators that block PR Ser294 phosphorylation as part of rational combination (i.e., with antiestrogens) endocrine therapies designed to durably block breast cancer recurrence.
2017-04-10 | GSE94363 | GEO
Project description:SNP data for Ovarian cancer PRS (cases)
| EGAD00001008143 | EGA
Project description:Frequent loss of heterozygosity (LOH) at 11q22-23 in breast cancer strongly suggests that this region contains a tumor suppressor gene, yet to be identified. We and others have shown Yes-associated protein (YAP), which is located at 11q22.2, transactivates the p53 family member p73 upon DNA damage, suggesting a tumor suppressive function for YAP. Our analysis of breast tumor tissues by immunohistochemistry (IHC) showed loss of YAP protein expression in great portion of breast cancers. We used microarray to look at the targte genes regulated by YAP in normal breast luminal cell and breast cancer cell lines. Experiment Overall Design: We generated stable cell lines by introducing control vector(pRS-IRES-GFP/pmig) or YAP shRNA(pRS-IRES-GFP-YAP/pmig-YAP) in a normal breast luminal cell line 1089 luminal and breast cancer cell lines MDA MB231. RAN was extracted and hybridized on Affymetrix microarrays.We looked for new target genes regulated by YAP in normal breast luminal cell and breast cancer cell lines.
2009-01-18 | E-GEOD-7700 | biostudies-arrayexpress