p73 is a p53 family transcription factor that plays critical roles during development and tumor suppression. We analyzed p73 activity using a combination of ChIP-on-Chip and gene expression profiling, both at baseline and after treatment with the mTOR inhibitor rapamycin.
Differential regulation of the p73 cistrome by mammalian target of rapamycin reveals transcriptional programs of mesenchymal differentiation and tumorigenesis.
Treatment
View SamplesThe integral role of p53 in tumor suppression has promted many laboratories to perform extensive analyses of signaling pathways downstream of the p53 family of sequence-specific DNA binding transcription factors (p53 and its homologs p63 and p73). Despite the ability of p73 to regulate many p53 family target genes, little is known about the specific pathways that modulate p73 during development, tumorigenesis and tumor therapy. In this study we present a gene signature-based approach for connecting signaling pathways to transcription factors, as exemplified by p73. We generated a p73 gene signature by integrating whole-genome chromatin immunoprecipitation and expression profiling.
A gene signature-based approach identifies mTOR as a regulator of p73.
No sample metadata fields
View SamplesThe integral role of p53 in tumor suppression has promted many laboratories to perform extensive analyses of signaling pathways downstream of the p53 family of sequence-specific DNA binding transcription factors (p53 and its homologs p63 and p73). Despite the ability of p73 to regulate many p53 family target genes, little is known about the specific pathways that modulate p73 during development, tumorigenesis and tumor therapy. In this study we present a gene signature-based approach for connecting signaling pathways to transcription factors, as exemplified by p73. We generated a p73 gene signature by integrating whole-genome chromatin immunoprecipitation and expression profiling.
A gene signature-based approach identifies mTOR as a regulator of p73.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Loss of the polycomb mark from bivalent promoters leads to activation of cancer-promoting genes in colorectal tumors.
Specimen part, Disease, Subject
View SamplesBackground: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers.
Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.
Sex, Age, Specimen part, Disease
View SamplesAnalysis of expression changes between colon tumors (Duke's stage II) and matching colon mucosa tissues using Affymetrix GeneChip Human Gene 2.0 ST arrays.
Loss of the polycomb mark from bivalent promoters leads to activation of cancer-promoting genes in colorectal tumors.
Specimen part, Disease, Subject
View SamplesIntroduction: microRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in earlier stages, we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression would also be found in early breast neoplasias. Methods: Expression profiling of 365 miRNAs by RT-qPCR was combined with laser-capture microdissection to obtain an epithelial specific miRNA expression signature of normal breast epithelium (n=9) and of paired samples of histologically normal epithelium (HN) and ductal carcinoma in situ (DCIS) (n=16). To determine how miRNAs may control the expression of co-dysregulated mRNAs we also performed gene expression microarray analysis in the same paired HN and DCIS samples and integrated this with miRNA-target prediction. We further validated several target pairs by modulating the expression levels of miRNAs in MCF7 cells and measured the expression of target mRNAs and proteins. Results: Thirty-five miRNAs were aberrantly expressed between RM, HN and DCIS. Twenty-nine miRNAs and 420 mRNAs were aberrantly expressed between HN and DCIS. Combining these two datasets with miRNA-target prediction we identified two established target pairs (miR-195:CCND1 and miR-21:NFIB) and tested several novel miRNA:mRNA target pairs. Over-expression of the putative tumor-suppressor miR-125b, under-expressed in DCIS, repressed the expression of MEMO1, which is required for ErbB2-driven cell motility (also a target of miR-125b); and NRIP1/RIP140, which modulates the transcriptional activity of the estrogen receptor. Knockdown of the putative oncogenic miRNAs miR-182 and miR-183, both highly over-expressed in DCIS, increased the expression of CBX7 (which regulates E-cadherin expression), DOK4, NMT2, and EGR1. Augmentation of CBX7 by knockdown of miR-182 expression, in turn, positively regulated the expression of E-cadherin, a key protein involved in maintaining normal epithelial cell morphology which is commonly lost during neoplastic progression. Conclusions: These data provide the first miRNA expression profile of normal breast epithelium and of pre-invasive breast carcinoma. Further, we demonstrate that altered miRNA expression can modulate gene expression changes that characterize these early cancers. We conclude that miRNA dysregulation likely plays a substantial role in early breast cancer development.
Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.
Sex, Age, Specimen part, Disease
View SamplesMultiple Sclerosis (MS) is an immune-mediated chronic inflammatory disease affecting the central nervous system. The cause of MS is not known and the mechanism of IFN-beta, a disease-modifying treatment (DMT) approved for MS, is not well-understood. Oligonucleotide microarrays were used to study gene expression in plasmacytoid denditic cells (pDCs) which are antigen-presenting cells implicated in MS pathogenesis.
Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesIn two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.
No sample metadata fields
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