Purpose:
Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia.
Treatment
View SamplesSignal transduction processes mediated by phosphatidyl inositol phosphates affect a broad range of cellular processes such as cell cycle progression, migration and cell survival. The protein kinase AKT is one of the major effectors in this signaling network. Chronic AKT activation contributes to oncogenic transformation and tumor development. Therefore, new small drugs were designed to block AKT activity for cancer treatment.
Characterization of AKT independent effects of the synthetic AKT inhibitors SH-5 and SH-6 using an integrated approach combining transcriptomic profiling and signaling pathway perturbations.
Specimen part, Cell line
View SamplesProfiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2).
Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors.
Cell line
View SamplesTo attain deeper insight into metabolic alterations in Trpm7 gene deficient mice we used microarrays for profiling of transcripts in villi of Trpm7 ko and control mice.
TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival.
Sex, Age
View SamplesSimilar to the bone marrow, the mammary gland contains a distinct population of Hoechst-effluxing side population cells, MG-SPs. To better characterize MG-SPs, their microarray gene profiles were compared to the remaining cells, which retain Hoechst dye (MG-NSPs). For analysis, gene ontology (GO) that describes genes in terms of biological processes and ontology traverser (OT) that performs enrichment analysis were utilized. OT showed that MG-SP specific genes were enriched in the GO categories of cell cycle regulation and checkpoints, multi-drug resistant transporters, organogenesis, and vasculogenesis. The MG-NSP upregulated genes were enriched in the GO category of cellular organization and biogenesis which includes basal epithelial markers, p63, smooth muscle actin (SMA), myosin, alpha-6 integrin, cytokeratin (CK) 14, as well as luminal markers, CK8 and CD24. Additional studies showed that a higher percentage of MG-SPs exist in the G1 phase of the cell cycle compared to the MG-NSPs. G1 cell cycle block of MG-SPs may be explained by higher expression of cell cycle negative regulatory genes such as TGF-beta2 (transforming growth factor-beta2), IGFBP-5 (insulin like growth factor binding protein-5), P18 INK4C and Wnt-5a (wingless-5a). Accordingly, a smaller percentage of MG-SPs expressed nuclear b-catenin, possibly as a consequence of the higher expression of Wnt-5a. In conclusion, microarray gene profiling suggests that MG-SPs are a lineage deficient mammary gland sub-population expressing key genes involved in cell cycle regulation, development and angiogenesis.
Transcriptional profiling of mammary gland side population cells.
No sample metadata fields
View SamplesInnate immunity is fundamental to recognition and clearance of bacterial infection. The relevant cells and molecules that orchestrate an effective response, however, remain incompletely understood. Here we describe a previously unknown population of B cells, which we have named innate response activator (IRA) B cells that recognize bacteria directly through TLR-4-MyD88 and protect against polymicrobial sepsis.
Innate response activator B cells protect against microbial sepsis.
Sex, Specimen part, Treatment
View SamplesThis series of samples comprises multiple early embryonic time courses for C. elegans. Time courses consisting of 10 time points each for 4 different genotypes are included: wild-type (strain N2 grown on E. coli strain OP50), pie-1(zu154) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain OP50), pie-1(zu154);pal-1(RNAi) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain HT115 expressing pal-1 hairpin RNA), and mex-3(zu155);skn-1(RNAi) (progeny of homozygous mutant mothers [Dpy] of strain JJ518 grown on E. coli strain HT115 expressing skn-1 hairpin RNA). Embryos were manually staged by morphology at the 4-cell stage and allowed to develop in water for defined amounts of time at 22 degrees C. RNA was amplified as described (Baugh et al. Development, 2003; Baugh et al. Nucleic Acids Research, 2001). This series of samples comprises all replicate data reported by Baugh et al. (Development, 2005).
The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo.
No sample metadata fields
View SamplesSubstantial evidence implicates IGF-I signaling in the development and progression of breast cancer. To identify transcriptional targets of IGF action in breast cancer cells, we performed gene expression profiling (>22,000 RNA transcripts) of IGF-I-stimulated MCF-7 cells, a well characterized breast cancer cell line that is highly responsive to IGFs. We defined an IGF-I gene signature pattern of hundreds of genes either up-regulated or down-regulated at both 3 and 24 hrs in vitro. After removing genes considered generic to cell proliferation, the signature was examined in four different public profile datasets of clinical breast tumors (representing close to 1000 patients), as well as in profile datasets of experimental models for various oncogenic signaling pathways. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen, Ras, and PI3K/Akt/mTOR pathways. The IGF-I signature appeared activated in most estrogen receptor-negative (ER-) clinical breast tumors and in a substantial subset (~25%) of ER+ breast tumors. Patients with tumors showing activation of the IGF-I signature tended to have a shorter time to disease recurrence (including patients not receiving adjuvant therapy), both when considering all patients and the subset of ER+ patients. We found evidence for cross-talk and common transcriptional endpoints between the IGF-I and estrogen systems. Our results support the idea that the IGF-I pathway is one mechanism by which breast tumors may acquire hormone independence and a more aggressive phenotype.
Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis.
No sample metadata fields
View SamplesTo investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays.
Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts.
No sample metadata fields
View SamplesTo investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays.
Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts.
No sample metadata fields
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