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GSE26457
Homo sapiens
110 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is widely accepted that a womans lifetime risk of developing breast cancer at menopause is reduced by early full term pregnancy and multiparity. This phenomenon is associated with the development and differentiation of the breast, which ultimately imprints a specific genomic profile in the mammary epithelium. In the present work we demonstrate that this profile represents a permanent signature that could be associated with the breast cancer risk reduction conferred by pregnancy.
Publication Title
Defining the genomic signature of the parous breast.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Early genetic changes during cancer initiation may provide targets for agents that delay, or even prevent, cancer. We hypothesized that cells bearing a single inherited hit in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. Here, we report on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation-carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations that were independently validated by real-time RT-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers including, mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings demonstrate that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner, and that these detectable effects of one-hit represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention
Publication Title
Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in the developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.
Publication Title
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Lck-Dlx5 induces T-cell lymphoma but the mechanism is unknown.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogen deprivation using aromatase inhibitors is currently the standard of care for patients with estrogen-receptor (ER)-positive breast cancer. Unfortunately, prolonged estrogen deprivation leads to drug resistance (i.e. hormone-independent growth). We therefore used DNA microarray analysis to study the gene expression profiles of wild-type MCF-7 cells (which are sensitive to antihormone therapy) and long-term estrogen deprived MCF-7:5C and MCF-7:2A breast cancer cells (which are resistance to estrogen-deprivation; aromatase inhibitor resistant).
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Methylthioadenosine Phosphorylase (MTAP) is a tumor suppressor gene that encodes an enzyme responsible for the catabolism of the polyamine byproduct 5deoxy-5-methylthioadenosine (MTA). To elucidate the mechanism by which MTAP inhibits tumor formation, we have created isogenic MTAP+ and MTAP- HT1080 fibrosarcoma cells.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The study was designed to identify differentially expressed transcripts between wild type and Mtap heterozygous mice
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies.
Publication Title
Nestin Mediates Hedgehog Pathway Tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action.
Publication Title
Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Long non-coding RNAs (lncRNA) have emerged as important regulators of gene expression at both the transcriptional and post-transcriptional levels. While altered expressions of lncRNAs have been observed in breast cancer (BCa) development, their roles in BCa progression and metastasis are still poorly understood. To identify novel BCa-associated lncRNA candidates, we have employed a high-density SNP array based approach to uncover lncRNA genes at intergenic region that are aberrantly expressed in BCa. Here we report the role of a novel lncRNA, LincIN, in breast cancer progression and metastasis. High levels of LincIN expression are frequently observed in tumors compared to adjacent normal tissues, and are strongly associated with aggressive breast cancers. Importantly, analysis of The Cancer Genome Atlas (TCGA) data further suggested that high LincIN expression was associated with poor overall survival in patients with breast cancer (P<0.05). Our gain-and-loss experiments demonstrate that LincIN play a role in tumor cell migration and invasion and knockdown of LincIN diminishes tumor cell invasion in vitro and lung metastasis in a mouse xenograft model. We also identified a LincIN-binding protein complex, NF90/NF45, through which LincIN destabilizes tumor suppressor p21 mRNA post-transcriptionally and thereby represses its protein expression. In summary, our findings delineated an oncogenic role of LincIN in breast tumor progression-metastasis, and mechanistically uncovered its cooperative actions with NF90/NF45 in regulating tumor suppressor gene expression at the post-transcriptional level.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples