Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.
Expression of rearranged TCRgamma genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment.
Age, Specimen part
View SamplesIt 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.
Defining the genomic signature of the parous breast.
No sample metadata fields
View SamplesEarly 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
Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations.
Specimen part
View SamplesIt 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.
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
Specimen part
View SamplesLck-Dlx5 induces T-cell lymphoma but the mechanism is unknown.
No associated publication
Age, Specimen part
View SamplesEstrogen 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).
No associated publication
No sample metadata fields
View SamplesMethylthioadenosine 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.
No associated publication
Cell line, Treatment
View SamplesThe study was designed to identify differentially expressed transcripts between wild type and Mtap heterozygous mice
No associated publication
Sex, Specimen part
View SamplesThe 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.
Nestin Mediates Hedgehog Pathway Tumorigenesis.
Specimen part
View SamplesOnconase 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.
Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent.
Specimen part, Cell line
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