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GSE42331
Homo sapiens
64 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Patients with Klinefelter Syndrome have the karyotype 47,XXY. These men are suffering from hypergonadotropic hypogonadism and are infertile. It is debated whether the different hormonal constitution observed in these patients or different gene expression
Publication Title
Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Genes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal, immortalized, transformed and tumorigenic bronchial epithelial cells were identified. The differentially expressed genes were then analyzed to determine their relevance to the gene expression patterns of clinical non-small cell lung cancer (NSCLC) samples as well as the clinical outcome of patients with this disease.
Publication Title
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
Alternate Accession IDs
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 28 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- 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. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
Publication Title
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Alternate Accession IDs
Sample Metadata Fields
Age, 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.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Lung cancer is still the leading cause of cancer-related deaths in the US and worldwide. Understanding the global molecular profiles or transcriptome of lung cancers would strengthen our understanding of the biology of this malignancy.
Publication Title
ETS2 mediated tumor suppressive function and MET oncogene inhibition in human non-small cell lung cancer.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling using microarray technology.
Publication Title
Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
ETS2 is a canonical transcriptional factor and member of the ETS family of genes. ETS2 binds to consensus ERE binding sites in a broad spectrum of genes thus affecting many intracellular molecular functions. However, the role of ETS2 in the biology and pathogenesis of lung cancers is still not known.
Publication Title
ETS2 mediated tumor suppressive function and MET oncogene inhibition in human non-small cell lung cancer.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Treatment
View Samples