TC71 cells treated either with BEZ235 or DMSO
hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.
No sample metadata fields
View SamplesIn vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Using pathway signatures as means of identifying similarities among microarray experiments.
No sample metadata fields
View SamplesMany traditional cytotoxic agents used in the treatment of cancer function by eliciting an apoptotic response in tumor cells. However, evasion of apoptosis by BCL-2 family members is often deregulated prior to therapeutic intervention leading to treatment failure. To address this, ABT-737 was rationally designed to target BCL-2-like family members and has shown promising results against tumor cells dependent on BCL-2 for their survival. One shortcoming is that MCL-1, a member of the BCL-2 family is poorly inhibited by ABT-737 and is a major cause of resistance. To gain insight into biological pathways that could circumvent this resistance, we designed an shRNA screen to identify novel sensitizers to ABT-737 by engineering MYC driven lymphomas that were resistant to ABT-737 due to endogenous MCL-1 expression. Utilizing this model, we performed a shRNA drop-out screen and identified Dhx9 as a target whose suppression sensitizes cells to ABT-737. DHX9 loss lead to replicative stress signaling, which in turn potently induced the BH3-only proteins, NOXA and PUMA, in a p53-dependent manner to curtail MCL-1 activity. Induction of NOXA is essential for ABT-737 sensitization. Our results ascribe a novel role for DHX9 in the replicative stress pathway and link DHX9 activity to p53 function in vivo.
RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an Eμ-myc/Bcl-2 mouse model.
No sample metadata fields
View SamplesThe thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development.
Deletion of PKBalpha/Akt1 affects thymic development.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Cell line
View SamplesIn order to identify the effects of starvation on the PPP3R1 cell line trascriptome, we performed Affymetrix Gene-Chip hybridization experiments for the starved cells
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Cell line
View SamplesIn order to identify the effects of starvation on the MEFs wt trascriptome, we performed Affymetrix Gene-Chip hybridization experiments for the starved cells
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Cell line
View Samples1. To identify potential effectors responsible for anti-tumorigenesis by targeting PLD1, we performed microarray in two Wnt-relevant colon cancer cells and analyzed transcriptional profile of genes that were differently expressed by inhibition and knockdown of PLD1
Targeting phospholipase D1 attenuates intestinal tumorigenesis by controlling β-catenin signaling in cancer-initiating cells.
Specimen part, Cell line
View SamplesThe combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Overall design: 16 samples analyzed from 8 mice (each mouse was bearing two tumors, one on each flank) in 4 treatment groups (control, vemurafenib alone, JQ1 alone, JQ1+vemurafenib)
BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.
Cell line, Treatment, Subject
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
No sample metadata fields
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