Coordinate expression of the somatic cell reprogramming factors Oct4, Sox2, Klf4 and c-Myc within embryonic stem cells preserves the self-renewal of these cells, while allowing for the expression epitope tagged Sox2. Taking advantage of this observation, we engineered embryonic stem cells (i-OSKM-ESC) to inducibly express Oct4, Klf4, c-Myc and an epitope tagged form of Sox2 from a polycistronic element, in the presence of doxycycline. We isolated Sox2 and its associated protein complexes by co-immunoprecipitation. Subsequently, we identified the Sox2-protein interactome in self-renewing embryonic stem cells using an unbiased proteomic screen (Multidimensional Protein Identification Technology [MudPIT]).
Determination of protein interactome of transcription factor Sox2 in embryonic stem cells engineered for inducible expression of four reprogramming factors.
Specimen part
View SamplesWe aimed to identify the gene network and pathway biology associated with neonatal sepsis by determining genome-wide alterations in host RNA in infected infants
Identification of a human neonatal immune-metabolic network associated with bacterial infection.
Sex, Specimen part
View SamplesWe determined gene expression profiles which were induced in the chick chorio-allantoic membrane 24 h after application of recombinant human VEGF.
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
No sample metadata fields
View SamplesThe QSi5 inbred strain of mice was established from an outbred Quackenbush-Swiss strain by full-sib inbreeding and selection on the basis of increased litter size and shortened inter-litter interval in the Department of Veterinary Physiology (later REPROGEN) , University of Sydney (Holt et al., 2004). The strain has an average litter size of more than 13 pups, and females commonly nurse up to 18 pups with greater than 90% survival to weaning. Along with an increased body weight (BW), these traits are clearly indicative of enhanced lactation performance (Knight et al., 1986). Indeed lactation performance, assessed by a weigh-suckle-weigh method, was 3-fold greater in QSi5 mice than the CBA strain (Riley et al., 2006). In this study, we utilize the divergent phenotypes of QSi5 and CBA/CaH mice to identify genes associated with enhanced mammary gland capacity.
Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice.
No sample metadata fields
View SamplesThis study compares a cell line (MDA-MB-468GFP-LN) that aggressively metastasizes to lymph nodes to its parental line MDA-MB-468GFP. Derivation of the lines is described in Vantyghem et al, Clinical & Experimental Metastasis (2005) 22: 351361. The goal here was to compare the gene expression profile of MDA-MB-468GFP-LN to MDA-MB-468GFP, Compare differential expression to databases of genes known to be involved in either cancer stem cell identification or lymph node specific metastasis in large scale clinical studies, and to confirm genes by RT-PCR
Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment.
No sample metadata fields
View SamplesEstrogen-responsive genes were identified by transcript profiling of estrogen-treated MCF-7 breast cancer cells.
Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.
No sample metadata fields
View SamplesProlactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5 we made an inducible Elf5 sh-RNA knock down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin-induction of Elf5 expression tempered the anti-proliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5.
Disease, Cell line, Treatment
View Samples19 paired human left ventricular apex samples were harvested at the time of implant of a left ventricular assist device (PRE) and at the time of explant (POST). The cohort included patients that were clinically classified as "ischemic" (I) showing evidence of coronary artery disease, "non-ischemic" (N) no evidence of coronary artery disease or "acute Myocardial infarction" (IM) myocardial infarction within 10 days of the implant. Tissue was processed and hybridized to the Affymetrix HG-U133A chip.
Genomic profiling of the human heart before and after mechanical support with a ventricular assist device reveals alterations in vascular signaling networks.
No sample metadata fields
View SamplesThe HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature and acquisition of a self renewing phenotype independent of an EMT programme or regulation of cancer stem cell markers. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in patients receiving adjuvant chemotherapy (but not targeted anti-HER2 therapy), MYC amplification is associated with a poor outcome in HER2+ breast cancer patients. These findings demonstrate the importance of molecular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have important diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.
c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer.
Sex, Specimen part, Cell line
View SamplesDclk1 (Doublecortin like kinase-1) labels a rare population of long-lived and largely quiescent cells in the adult mouse pancreas. The expression of Dclk1+ vs Dclk1- pancreatic cells (mostly acinar) is observed. Overall design: Dclk1+ vs Dclk1-
Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis.
Specimen part, Cell line, Subject
View Samples