The aim of this experiment was to get a comparison of the signatures between a non-transformed cell (NIH3T3 + vector) and a transformed cell (NIH3T3 + Fbxo7). NIH3T3 cells become transformed after the stable integration of the Fbxo7 gene. Fbxo7 potentiates cyclin D/cdk6 activity.
Transforming activity of Fbxo7 is mediated specifically through regulation of cyclin D/cdk6.
Cell line
View SamplesCompare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Age, Specimen part
View SamplesIdentification of the relationships of Kaposi sarcoma (KS), normal skin to various cell cultures. The effects of KS herpes virus, the infectious cause of KS, on infected endothelial cells are also investigated.
ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma.
Sex, Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesThe most frequent genetic alterations in melanoma are gain-of-function mutations in BRAF, which result in addiction to the RAF-MEK-ERK signaling pathway. Despite success of RAF and MEK inhibitors in treating BRAFV600 mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, we generated isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells by overexpression of ERK2. Using this model system, we demonstrated that supra-physiological levels of MAPK signaling led to cell death, which was reversed by MAPK inhibitors. Whereas MAPK pathway inhibition led to cell stasis in BRAFV600E melanoma cells, MAPK hyperactivation induced cytotoxicity. Furthermore, complete tumor regression was observed in an ERK2 overexpressing xenograft model. To identify mediators of MAPK hyperactivation- induced cell death, we conducted a large-scale pooled screen which showed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wildtype melanoma were sensitive to this perturbation. This vulnerability to MAPK hyperactivation raises the possibility of a novel therapeutic approach for RAS/RAF mutant cancers.
No associated publication
Sex, Specimen part, Disease, Cell line, Treatment
View SamplesWe established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Prenatal origin of separate evolution of leukemia in identical twins.
Sex, Specimen part, Disease, Disease stage
View SamplesType-1 interferons are critical for inhibiting HIV and simian immunodeficiency virus. However, it is largely unknown which of the hundreds of interferon-stimulated genes (ISGs) restrict HIV replication (with the notable exceptions of APOBEC3G, MX2, and BST-2). To identify HIV restriction factors, we sequenced activated CD4+ T cell RNA from 19 humans with untreated HIV infection before and after peginterferon alpha 2b (IFN) injection. Antiretroviral therapy (ART) durably suppresses HIV-1, prevents progression to acquired immunodeficiency syndrome, and reduces mortality. However, even with ART HIV-1 infected adults remain at higher risk of death from inflammatory disease. To understand the role of ART in altering cell-associated HIV RNA and host RNA changes within activated CD4 T cells we also sequenced activated CD4 T cell RNA from these same 19 humans after initiating ART and obtaining =12 weeks of undetectable viremia.
No associated publication
No sample metadata fields
View SamplesTo conduct clinical cancer research and study the genetic basis of hepatocellular carcinoma
No associated publication
No sample metadata fields
View SamplesTo facilitate preclinical translational science, this cohort of patient-derived xenograft (PDX) models of leukemia and lymphoma has undergone molecular characterization with whole transcriptome sequencing, targeted exon sequencing of genes recurrently altered in leukemia and lymphoma, and other approaches. Here we provide the whole transcriptome sequencing data for these PDX models. Related molecular data and de-identified clinical information can be obtained at http://www.proxe.org.
No associated publication
No sample metadata fields
View SamplesMAP3K11 overexpression in tumors leads to weight loss in the host
No associated publication
Specimen part
View SamplesPost-chemotherapy relapse presents a major unmet medical need in AML where treatment options are limited. We used gene expression profile from 32 AML cell lines to characterize expression difference between responder and non-responders to PIM inhibitors. Our results highlight the importance of STAT5 and MYC in rendering cancer cells sensitive to PIM inhibitors.
No associated publication
Cell line
View Samples