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GSE14458
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. As a tool to investigate the biologic basis for metastasis in this model and to query the roles of specific genes in this signature, we isolated adenocarcinoma cell lines from these mice and used them to develop a syngeneic tumor model in wild-type littermates. Transcriptional profiling of the highly metastatic subcutaneous tumors revealed genes that regulate, among other processes, epithelial-to-mesenchymal transition and intra-tumoral inflammation and angiogenesis, whereas the non-metastatic tumors did not.
Publication Title
Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here we addressed this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. A feature of metastasis-prone tumor cells that distinguished them from metastasis-incompetent tumor cells was plasticity in response to changes in their microenvironment. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in 3-dimensional culture that underwent epithelial-mesenchymal transition (EMT) following treatment with transforming growth factor-beta or injection into syngeneic mice. This plasticity was entirely dependent upon the microRNA-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that microenvironmental cues direct tumor metastasis by regulating miR-200 expression.
Publication Title
Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cells that give rise to metastatic disease are a primary cause of cancer-related death and have not been fully elucidated in patients with lung cancer. Here, we addressed this question by using tissues from a mouse that develops metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. We identified a metastasis-prone population of tumor cells that differed from those with low metastatic capacity on the basis of having sphere-forming capacity in Matrigel cultures, increased expression of CD133 and Notch ligands, and relatively low tumorigenicity in syngeneic mice. Knockdown of jagged1 or pharmacologic inhibition of its downstream mediator phosphatidylinositol 3-kinase abrogated the metastatic but not the tumorigenic activity of these cells. We conclude from these studies on a mouse model of lung adenocarcinoma that CD133 and Notch ligands mark a population of metastasis-prone tumor cells and that the efficacy of Notch inhibitors in metastasis prevention should be explored.
Publication Title
The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitogen-activated protein kinase kinase 4 (MKK4) is a dual-specificity kinase activated by environmental stress, cytokines, and peptide growth factors that reportedly can promote or inhibit tumor cell growth and metastasis. Somatic mutations in the gene encoding MKK4 (MAP2K4) have been identified in various human cancers, but the consequences of these mutations on MKK4 function and the biology of tumor cells that have them have not been elucidated. Here we report that, of the eleven mutations within the MAP2K kinase domain described thus far, one had gain-of-function (Q142L) and six had loss-of-function. Three of the loss-of-function mutations are nonsense mutations that produced C-terminally-truncated proteins (I295fs*23, R304*, and W310*) that were highly ubiqitinated and rapidly degraded when introduced into cells, and three are missense mutations in the ATP-binding pocket (N234I), activation loop (S251N), or C-lobe (P326L). We modeled the consequences of MAP2K4 loss-of-function mutations on cells by introducing MKK4 short-hairpin RNA constructs and found that MKK4 depletion enhanced the ability of a weakly tumorigenic murine cancer cell to metastasize when injected into syngeneic mice but had no effect on primary tumor formation. MKK4-depleted cells exhibited an increased capacity to migrate across PET filters and to invade through matrigel but no change in anchorage-dependent or -independent proliferation. Transcriptional profiling of these cells revealed gene expression changes that promote epithelial-to-mesenchymal transition and angiogenesis. We conclude that MKK4 inactivation promoted metastasis but not primary tumor formation. Collectively, these findings implicate loss-of-function MAP2K4 somatic mutations in tumor metastasis and provide one of the few examples of a somatic mutation in cancer cells that exerts a metastasis-specific effect.
Publication Title
Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing peroxisome proliferator-activated receptor γ2 expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To gain insight into EMT-independent biological processes through which PI3K promotes invasion, RNA samples from 344SQ_p110 shRNA cells and 344SQ_scr cells were subjected to global transcriptional profiling.
Publication Title
ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During malignant disease progression, the extracellular matrix (ECM) of epithelial tumors accumulates inter-molecular cross-links between collagen strands; these cross-links enhance ECM stiffness and trigger tumor cell invasion and dissemination, but the mechanisms that regulate intra-tumoral collagen maturation have not been fully defined. Using a new mouse model of metastatic lung adenocarcinoma driven by mutant K-ras expression and Cdkn1a inactivation, we showed that tumor cell invasion and metastasis are driven by high expression of lysyl hydroxylase 2 (LH2), an enzyme that hydroxylates telomeric lysine (Lys) residues on collagen.
Publication Title
Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Signal transduction processes mediated by phosphatidyl inositol phosphates affect a broad range of cellular processes such as cell cycle progression, migration and cell survival. The protein kinase AKT is one of the major effectors in this signaling network. Chronic AKT activation contributes to oncogenic transformation and tumor development. Therefore, new small drugs were designed to block AKT activity for cancer treatment.
Publication Title
Characterization of AKT independent effects of the synthetic AKT inhibitors SH-5 and SH-6 using an integrated approach combining transcriptomic profiling and signaling pathway perturbations.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The objective of the present study was to identify genes that are involved in increasing the ovulation number in mouse line FL1 that had been selected for high fertility performance.
Publication Title
Expression profiling of a high-fertility mouse line by microarray analysis and qPCR.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
mRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients.
Publication Title
Constitutive upregulation of the transforming growth factor-beta pathway in rheumatoid arthritis synovial fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 251 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukemia (AML) is a heterogeneous disease and AML with normal karyotype (AML-NK) is categorized as an intermediate-risk group. Over the past years molecular analyses successfully identified biomarkers that will further allow to dissecting clinically meaningful subgroups in this disease. Thus far, somatic mutations were identified which elucidate the disturbance of cellular growth, proliferation, and differentiation processes in hematopoietic progenitor cells. In AML-NK, acquired gene mutations with prognostic relevance were identified for FLT3, CEBPA, and NPM1. FLT3-ITD mutations were associated with short relapse-free and overall survival, while mutations in CEBPA or NPM1 (without concomitant FLT3-ITD) had a more favorable outcome.
Publication Title
Quantitative comparison of microarray experiments with published leukemia related gene expression signatures.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples