In order to obtain a global picture regarding regulation of p53 in liver cells we used HepG2 hepatoma cells.We created two isogenic sub-cultures of HepG2 cells with altered expression of p53.
Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53.
Specimen part, Cell line
View SamplesHuman mononuclear cells were cultured in 2 phases. In the 1st phase the culture medium contained cyclosporine A the 2nd phase contained SCF and erythropoietin. Cells were collected at 3 stages of differentiation; on day 6, 10, 12 and represented early erythroblasts, medium stage and normoblasts.
Identification of gene networks associated with erythroid differentiation.
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View SamplesRecently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior.
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
Specimen part, Cell line
View SamplesWe show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Specimen part, Cell line, Subject
View SamplesDuplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification.
Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues.
Specimen part, Cell line
View SamplesDNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. We show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using in vitro evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average. The data indicate that changes in population-averaged methylation occur through a stochastic process that generates a stream of local and uncorrelated methylation aberrations. Despite the stochastic nature of the process, nearly deterministic epigenetic remodeling emerges on average at loci that lose or gain resistance to methylation accumulation. Changes in the susceptibility to methylation accumulation are correlated with changes in histone modifications and CTCF occupancy. Characterizing epigenomic polymorphism within cell populations is therefore critical for understanding methylation dynamics in normal and cancer cells.
Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues.
Specimen part, Cell line
View SamplesA prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
A Transcriptional Lineage of the Early C. elegans Embryo.
Specimen part, Subject
View SamplesComparisons of global gene-expression profiles revealed a greater distinction between CD4+ Treg cells and CD4+ conventional (Tconv) T cells residing in abdominal (epidydimal) fat versus in more standard locations such as the spleen, thymus and LN.
Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters.
Specimen part
View SamplesEndometriosis, an estrogen-dependent, progesterone-resistant, inflammatory disorder affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Since the uterine lining (endometrium) in women with endometriosis has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n=148 archived endometrial samples from women with endometriosis or without endometriosis (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with endometriosis or no endometriosis involved two binary decisions each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no endometriosis from endometriosis, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified endometriosis with 90-100% accuracy, were cycle phase-specific or independent, and utilized relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism and growth factor signaling in endometrium of women with endometriosis. Similar findings were observed with other disorders versus controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic endometriosis with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate-genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of endometriosis and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue.
Molecular classification of endometriosis and disease stage using high-dimensional genomic data.
Specimen part
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