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GSE137915
Homo sapiens
19 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer entities including hepatocellular carcinoma (HCC). However, to which extent YAP and TAZ contribute to liver tumorigenesis via common and exclusive molecular mechanisms is poorly understood. RNAinterference (RNAi) experiments illustrate that YAP and TAZ individually support HCC cell viability and migration, while for invasion additive effects were observed. Comprehensive expression profiling revealed partly overlapping YAP/TAZ target genes as well as exclusively regulated genes.
Publication Title
TAZ target gene ITGAV regulates invasion and feeds back positively on YAP and TAZ in liver cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Total RNA was isolated from HuH-7 cells after transfection of IGF-II specific siRNAs. Gene expression profiling was performed using the Affymetrix Human Genome U133A 2.0 Arrays. The raw data were analysed using mixed model ANOVA.
Publication Title
Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
Illumina HiSeq 2500
Description
Depletion of immunosuppressive tumor-associated macrophages (TAM) or reprogramming towards a pro-inflammatory activation state represent different strategies to therapeutically target this frequent myeloid population. Here we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAM to profound reprogramming in the presence of a CD40 agonist prior to their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R/CD40 stimulation of macrophages is sufficient to trigger a productive and durable T cell response in various mouse cancer models. The central role of macrophages in regulating T cell-dependent tumor rejections was substantiated by depletion experiments and transcriptomic analysis of ex vivo sorted TAM. Since CD40 expression on human TAM varies between different tumor types, co-expression of human CSF-1R and CD40 in colorectal adenocarcinoma and mesothelioma can serve as criteria to select these tumor types for clinical development Overall design: Female C57BL/6N mice (6-8 weeks in age, obtained from Charles River) were inoculated with 106 MC38 colorectal adenocarcinoma tumor cells subcutaneously. Tumor growth curves were monitored by caliper measurement and once tumor size reached 250 mm3 in average, groups were allocated for antibody treatment. Ten mice/group were treated with 30 mg/kg IgG1 isotype control antibody clone MOPC-21 (BioXCell), 4 mg/kg anti-CD40 rat IgG2a antibody clone FGK45 (BioXCell), 30mg/kg anti-CSF-1R antibody clone 2G2, 4 mg/kg rat IgG2a control clone 2A3 (BioXCell). For depletion experiments 4mg/kg mouse anti-CD4 antibody clone GK1.5 (Biolegend), 4mg/kg anti-NK1.1 antibody clone PK136 (BioXCell) and 4mg/kg anti-CD8a antibody clone 53-6.7 (BioXCell) were administered when tumor size reached 190mm3 in average. Antibodies were given every second day for four times. In between doses two and three of the depleting antibodies, animals were further treated with vehicle control (0,9% sodium saline), MOPC21, FGK45, 2G2 or combination of FGK45 and 2G2. The anti-CSF-1R antibody or respective IgG1 control antibody were administered weekly until tumors regressed completely or animals reached termination criteria, while the anti-CD40 antibody was only administered once at day 11 simultaneously with the anti-CSF-1R antibody. All antibodies were given intraperitoneally. All procedures were performed in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and European Union directives and guidelines.
Publication Title
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA
Publication Title
Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. In order to identify underlying commonalities in gene transcription associated with the phenotype, we compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant S1 cells that form polarized spheres (acini), the malignant T4-2 cells that form large tumor-like clusters, and the phenotypically reverted T4-2 cells that polarize as a result of correction of the microenvironmental signaling.
Publication Title
Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
26972c yeast cells were transformed with either empty vector (pYES3) or pYES3:Gm:bHLHm1. Cells were grown on low ammonium concentrations to observe transcriptional changes in the yeast genome in response to the soybean bHLHm1 transcription factor.
Publication Title
Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We analyzed gene expression in 184 (finite life span) and HMT3522 S1 (immortal non-malignant) HMECs on successive days (3, 5, and 7) post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7.
Publication Title
Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer.
Sample Metadata Fields
Sex, Specimen part, Cell line, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nonmalignant human mammary epithelial cells (HMEC) seeded in laminin-rich extracellular matrix (lrECM) form polarized acini and, in doing so, transit from a disorganized proliferating state to an organized growth-arrested state. We hypothesized that the gene expression pattern of organized and growth-arrested HMECs would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in 184 (finite life span) and HMT3522 S1 (immortal nonmalignant) HMECs on successive days after seeding in a lrECM assay. Both HMECs underwent growth arrest in G0-G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines and examined the expression of these genes in a previously published panel of microarray data for 295 breast cancer samples. We show that genes that are significantly lower in the organized, growth-arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.
Publication Title
Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGFbeta (0.4 ng/ml), or double-treated. All double-treated (IR+TGFbeta) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, beta-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, even though IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.
Publication Title
Ionizing radiation predisposes nonmalignant human mammary epithelial cells to undergo transforming growth factor beta induced epithelial to mesenchymal transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
The mechanisms underlying hepatoblastoma are not well defined. To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing. Hepatoblasoma was histologically confirmed. Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children. Overall design: Hepatic mRNA profiles of normal (n=3), background (n=6), and hepatoblastoma (n=23) tissues were generated through RNAsequencing using the Illumina HiSeq2500.
Publication Title
PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples