Atf1 was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Genome wide transcription profiling reveals a major role for the transcription factor Atf1 in regulation of cell division in Schizosaccharomyces pombe.
No sample metadata fields
View SamplesTumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Specimen part, Cell line, Treatment
View SamplesDuring the past two decades although many genes e.g.,Gdf5, Wnt9a, Noggin etc. have been identified and characterized in joint development, still a comprehensive understanding of molecular network operational in articular cartilage morphogenesis is far from being drawn. This might be due to incompleteness in the number of molecules identified.
A comprehensive mRNA expression analysis of developing chicken articular cartilage.
Specimen part
View SamplesWe demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis, but how this is achieved is largely unknown. To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls.
Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis.
Specimen part, Time
View SamplesWe have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
No sample metadata fields
View SamplesPurpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 158 TN tumors (54 AA) from The Cancer Genome Atlas (TCGA). Meta-analyses were performed to obtain summary estimates by combining TCGA and Detroit AA cohort results. Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR)=1.56, 95% confidence interval (CI) 1.31-1.86, nominal p=5.1x10-7, FDR p=0.014], SPIC [HR=1.47, 95%CI 1.26-1.73, nominal p=1.8x10-6, FDR p=0.022], and MIR4311 [HR=1.57, 95% CI 1.31-1.92, nominal p=2.5x10-5, FDR p=0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. Meta-analysis with TCGA data showed that CLCA2 and SPIC were associated with overall survival for TNBC among AA women. Conclusions: We identified three potential prognostic markers for TNBC in AA women, for which SPIC may be an AA-specific prognostic marker.
CLCA2 expression is associated with survival among African American women with triple negative breast cancer.
Age, Treatment, Race
View SamplesThe origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each others metastatic behavior.
Isolation and characterization of a metastatic hybrid cell line generated by ER negative and ER positive breast cancer cells in mouse bone marrow.
Specimen part, Cell line
View SamplesRecent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance. Overall design: RNA-Seq of laser microdissection of motor neuron bodies from two biological replicates each of SOD1 YFP (wildtype 592) and SOD1 G85R YFP (737) transgenic mice.
RNA-Seq profiling of spinal cord motor neurons from a presymptomatic SOD1 ALS mouse.
Age, Specimen part, Cell line, Subject
View SamplesUsing a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
No sample metadata fields
View SamplesPerinatal exposure to bisphenol A (BPA) has been shown to cause aberrant mammary gland morphogenesis and mammary neoplastic transformation. Yet, the underlying mechanism is poorly understood. We tested the hypothesis that mammary glands exposed to BPA during a susceptible window may lead to its susceptibility to tumorigenesis through a stem-cell mediated mechanism. We exposed 21-day-old Balb/c mice to BPA by gavage (25 µg/kg/day) during puberty for 3 weeks, and a subset of animals were further challenged with one oral dose (30 mg/kg) of 7,12-dimethylbenz[a]anthracene (DMBA) at 2 months of age. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age for mammary stem cell (MaSC) quantification and function analysis. Pubertal exposure to the low-dose BPA increased lateral branches and hyperplasia in adult mammary glands and caused an acute increase of MaSC in 6-week-old glands and a delayed increase of luminal progenitors in 4-month-old adult gland. Most importantly, pubertal BPA exposure altered the function of MaSC from different age groups, causing pre-neoplastic lesions in their regenerated glands similar to those induced by DMBA exposure, which indicates that MaSCs are susceptible to BPA-induced transformation. Deep sequencing analysis on MaSC-enriched mammospheres identified a set of aberrantly expressed genes associated with pre-neoplastic lesions in human breast cancer patients. Thus, our study for the first time shows that pubertal BPA exposure altered MaSC gene expression and function such that they induced early neoplastic transformation. Overall design: Four samples were analyzed (control, BPA, DMBA, BPA+DMBA), and for each treatment group, mammospheres from 5 animals were pooled for RNA extraction.
Pubertal bisphenol A exposure alters murine mammary stem cell function leading to early neoplasia in regenerated glands.
Age, Specimen part, Treatment, Subject
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