gene expression analysis ussing microarray analysis of a subset of primary tumors collected from patients that participated in the CONFIRM phase III study, which randomized post menopausal patients with ER+ metastatic breast cancer to fulvestrant 500mg and fulvestrant 250mg.
No associated publication
Age, Specimen part
View SamplesAs part of a large genetic evolution study we also acquired 3'UTR expression arrays at two time points for the same 18 patients with CLL.
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesIdentification of BRD32048 as an inhibitor of ETV1 oncogenic transcription factor. This compound was indentified by small molecule mcroarray (a binding assay). It was able to consistently inhibit an ETV1-dependent MMP1-driven luciferase signal. Its direct binding was validated by Suface plasmon resonance (Biacore assay). It inhibits ETV1-driven invasion in ETV1-dependent cell lines. The goal of this gene expression comparison was to interogate the effects of BRD32048 on the global gene expression and to define the degree to which its siganture overlaps with an ETV1-specific shRNA-induced gene expression signature.
No associated publication
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.
Specimen part
View SamplesThe complexity of RAS signaling makes targeting RAS challenging. We therefore hypothesized that inhibiting a combination of downstream targets of RAS may potentially lead to an effective therapeutic intervention. We performed a high-throughput chemical screen using a library consisting of multi-targeted inhibitors with the expectation that one or more inhibitors would likely- due to their broad spectrum inhibitory potential- hit critical targets of mutant NRAS. We identified GNF-7, a multi-targeted kinase inhibitor that proved to have high selectivity and sensitivity for leukemia cells with NRAS mutations both in vitro and in vivo.
No associated publication
Age, Specimen part
View SamplesGlioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFR and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of PDGFR and the analysis of GBM signaling pathways using proteomics. We discovered the tubulin-binding protein Stathmin1 (STMN1) as a PDGFR phospho-regulated target and that this mis-regulation conferred selective sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFR GBMs with VB in mice drastically prolonged survival and was dependent on STMN1. Our work provides a rationale for evaluating genotype-specific anti-microtubule drugs as cancer treatment in select GBM patient populations.
A PDGFRα-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine.
Specimen part, Treatment
View SamplesChildren with Down syndrome (DS) have a 20-fold increased risk of developing B cell acute lymphoblastic leukemia (B-ALL). Polysomy 21 (i.e., extra copies of chr.21) is also the most frequent somatic aneuploidy among all B-ALLs. Additional B-ALLs harbor intrachromosomal amplifications of chr.21q22 (iAMP21). Yet, the mechanistic links between chr.21q22 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chr.21q22 is sufficient to confer murine B cell self-renewal in vitro, B cell maturation defects in vivo, and B-ALL in concert with either BCR-ABL or CRLF2 with activated JAK2. Chr.21q22 triplication suppresses H3K27me3 in murine progenitor B cells and B-ALLs, and bivalent genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Strikingly, human B-ALLs with polysomy 21 are distinguished by their overexpression of genes known to be marked with H3K27me3 in multiple cell types. Finally, overexpression of HMGN1, a nucleosome remodeling protein encoded on chr.21q22, suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo. These data implicate HMGN1 overexpression and loss of H3K27me3 in progenitor B cell transformation and suggest strategies to target leukemias with polysomy 21.
Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.
No sample metadata fields
View SamplesmRNA expression was assayed from T47D SCR and T47D EGLN2 conditional knock down cell lines in order to profile the gene expression pattern regulated by EGLN2.
Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase.
Specimen part, Cell line
View SamplesHT-29 human colorectal adenocarcinoma cells were xenografted into both femoral regions of 6 to 8-week old Balb/c (nu/nu) mice. After 18 days electromagnetic heat treatment was performed.
No associated publication
No sample metadata fields
View SamplesNatural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored.
PLZF Controls the Expression of a Limited Number of Genes Essential for NKT Cell Function.
Sex, Specimen part
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