Mutant p53 proteins, resulting from the missense mutations of the TP53 tumor suppressor gene, possess gain-of-function activities and are among the most robust oncoproteins in human tumors. They are potentially important therapeutic targets. No studies to date have distinguished common, therapeutically relevant mutant p53 gain-of-function effects from effects specific to different mutant variants and cell backgrounds. here we performed RNA-seq analysisin MDA-MB-231 (R280K) upon silencing TP53 or the control siRNA. Overall design: MDA-MB-231 (R280K) cell line was transfected with control or p53 siRNA.So The study comprises one experimental cell line,in triplicate.
Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer.
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View SamplesWe constructed a primary lung cell model to permit regulated expression of KRASG12D. To do this, we leveraged a non-transformed, immortalized, human primary bronchial epithelial cell line (HBEC; hTert, CDK4, TP53 knockdown) that remains anchorage dependent and do not develop tumors when implanted into mice. We next modified these cells by stably integrating a regulatable KRASG12D allele, iKRASG12D, such that physiological expression of mutant KRAS is activated upon addition of doxycycline. The HBEC-iKRAS (WT) cell line and HBEC-iKRASG12D (MUT) cell line were propagated with or without Doxycycline (500ng/ml) respectively. RNA profiling of HBEC-iKRASG12D and HBEC-iKRASWT cells revealed widespread changes for HBECs harboring the activated KRAS allele in the presence of Dox. Within the KRASG12D-induced genes, the Molecular Signatures Database identified the oncogenic RAS signature as a top-enriched gene set. Upregulation of Ras signaling in Dox-treated HBEC-iKRASG12D cells was also supported by a significant overlap with a KRAS signature previously characterized by Singh et al.
In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer.
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View SamplesEpstein-Barr virus is associated with several human malignancies, including Burkitt Lymnphoma. The virus encodes more than 40 microRNAs, which participate in its possible pathogenetic role.
Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus.
Specimen part, Cell line
View SamplesThe subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 1 subunits, and thus contribute to neuronal excitability, neurotransmitter release and calcium-induced gene regulation. In addition certain subunits are targeted into the nucleus, where they directly interact with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual variants in specific neuronal functions. In the present study, an alternatively spliced 4 subunit lacking the variable N-terminus (4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGC) and modulates P/Q-type calcium currents in tsA cells and CaV2.1 surface expression in neurons. Compared to the other two known full-length 4 variants (4a, 4b) 4e is most abundantly expressed in the distal axon, but lacks nuclear targeting properties. To examine the importance of nuclear targeting of 4 subunits for transcriptional regulation, we performed whole genome expression profiling of CGCs from lethargic mice individually reconstituted with 4a, 4b, and 4e. Notably, the number of genes regulated by each 4 splice variant correlated with the rank order of their nuclear targeting properties (4b> 4a> 4e). Together these findings support isoform-specific functions of 4 splice variant in neurons, with 4b playing a dual role in channel modulation and gene regulation, while the newly detected 4e variant serves exclusively in calcium channel-dependent functions.
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
Specimen part
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Resistance to CDK2 inhibitors is associated with selection of polyploid cells in CCNE1-amplified ovarian cancer.
Specimen part
View SamplesCyclin E1 (CCNE1) is amplified in various tumor types including high-grade serous ovarian cancer where it is associated with poor clinical outcome. We have demonstrate that suppression of the Cyclin E1 partner kinase, CDK2, induces apoptosis in a CCNE1 amplicon-dependent manner. Little is known of mechanisms of resistance to CDK inhibitors. We therefore generated OVCAR-3 sublines with reduced sensitivity to CDK2 inhibitors and profiled by gene expression microarrays.
Resistance to CDK2 inhibitors is associated with selection of polyploid cells in CCNE1-amplified ovarian cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
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View SamplesWe used microarrays to profile the expression levels of 285 ovarian samples in order to identify molecular subtypes of the tumour
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
No sample metadata fields
View SamplesWe used microarrays to profile the expression levels of 5 tumour samples
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
No sample metadata fields
View SamplesWe used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion.
LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin.
Sex, Specimen part, Subject
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