The effect of c-Myc over-expression on the sensitivity to Tipifarnib treatment in three cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210029 | GEO | 2022/08/01
REPOSITORIES: GEO
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Project description:Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progress. MIZ1, MYC-ER and MYC-ERVD ChIP-Seq with 10E2 and HC20 anti-ERalpha antibodies in MCF10A cells, performed on an Illumina IIx Genome Analyzer. Input sample is accessioned as GSM1423726.
2015-07-10 | E-GEOD-59146 | biostudies-arrayexpress
Project description:Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progr 4 different experimental conditions were analyzed: MYC-ER 4-OHT treated versus MYC-ER ctr-treated (EtOH), MYC-ER V394D 4-OHT treated versus MYC-ER V394D ctr-treated; 3 biological replicates for every condition.
2015-07-10 | E-GEOD-59145 | biostudies-arrayexpress
Project description:Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progress.
2015-07-10 | GSE59146 | GEO
Project description:Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progr
2015-07-10 | GSE59145 | GEO
Project description:Notch-targeted gamma-secretase inhibitors (GSIs) exhibited limited efficacy in glioblastoma patients. We identified that farnesyltransferase inhibitors (FTIs) increased sensitivity to GSIs in glioblastoma stem cells. To interrogate the mechanisms mediating the interaction between these two classes of compounds, we studied the impact on gene expression profiles by the combination of tipifarnib (FTI) and RO4929097 (GSI). We found that this combination treatment significantly suppressed genes implicated cell cycle progression. Real-time PCR validated the activities of tipifarnib to modulate expression of cell cycle regulators. We also showed that RO4929097 sensitized glioblastoma stem cells to compounds targeting some of these cell cycle regulators, such as AURKB and CDK4/6. These results suggest that regulation of cell cycle progression partially mediates the ability of FTIs to sensitize glioblastoma stem cells to GSIs.
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Project description:Purpose of this study was to compare the effect of c-myc over expression and acute high intensity muscle contraction on mRNA transcriptome in skeletal muscle
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Project description:The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3’ UTR analysis upon miR-17-19b overexpression. We identify over one hundred novel miR-17-19b targets, of which 40% are co-regulated by c-MYC. Down-regulation of a new miR-17/20 target Chek2 increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3’ UTR shortening at different stages of tumorigenesis.
2015-11-06 | PXD002810 | Pride
Project description:To identify proteomic signatures associated with hepatocellular carcinoma driven by MYC overexpression, proteomics was performed on the LAP-tTA/tetO-MYC mouse conditional liver cancer model. Upon MYC activation, mice form liver cancer. Differential proteomics was performed in "MYC on" (MYC-HCC) mouse liver tumors versus mouse control normal liver tissue (where MYC was not overexpressed to drive tumorigenesis -- "MYC off").
2022-10-12 | PXD031478 | Pride
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2020-06-30 | GSE135942 | GEO