We profiled primary breast cancer, nodal and liver metastatic tumours from three patients. At the time of initial diagnosis, all three patients presented with luminal breast cancer with adjacent nodal metastasis. They all received 5 years of enodrine therapy and all subsequently developed liver metastasis. Overall design: Examination of mRNA differences between primary, nodal and metastatic tumour samples.
Transcriptomic Profiling of Sequential Tumors from Breast Cancer Patients Provides a Global View of Metastatic Expression Changes Following Endocrine Therapy.
No sample metadata fields
View SamplesHypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
The l1-l2 regularization framework unmasks the hypoxia signature hidden in the transcriptome of a set of heterogeneous neuroblastoma cell lines.
Cell line
View SamplesThe Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis.
Induction of epithelial mesenchimal transition and vasculogenesis in the lenses of Dbl oncogene transgenic mice.
No sample metadata fields
View SamplesExperiment with 6 hybridizations, using 30 samples of species [Homo sapiens], using 6 arrays of array design [Affymetrix GeneChip Human Genome HG-U133A [HG-U133A]], producing 6 raw data files and 6 transformed and/or normalized data files.
Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene.
Specimen part, Disease
View SamplesDendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs. Immature DCs were differentiated in vitro from human monocytes under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and the gene expression profile was determined. Hi-DCs expressed novel hypoxia-inducible genes and were characterized by up-regulation of pathways associated with cell movement/migration.
Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.
No sample metadata fields
View SamplesDendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs and maturation into mature DCs. Mature DCs were differentiated in vitro from human monocytes under normoxic or hypoxic conditions and the gene expression profile was determined.
Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.
Specimen part, Disease, Treatment
View SamplesWe have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57Bl/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, while ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype.
Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke.
No sample metadata fields
View SamplesHypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Cell line
View SamplesUncontrolled Transforming growth factor-beta (TGF) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGF-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGF has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGF-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGF-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGF-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGF, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGF signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGF repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGF signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms.
The transcriptional regulators TAZ and YAP direct transforming growth factor β-induced tumorigenic phenotypes in breast cancer cells.
Cell line, Treatment
View SamplesSialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sex, Age, Specimen part
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