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Effects of 17-DMAG treatment on transcription in 4T1 cells populations resistant and non-resistant to 17-DMAG

ABSTRACT: Effects of 17-DMAG treatment on transcription in 4T1 cells populations resistant and non-resistant to 17-DMAG

PROVIDER: PRJNA896604 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22132725_1.fastq.gz	Fastqsanger.gz
	SRR22132725_2.fastq.gz	Fastqsanger.gz
	SRR22132726_1.fastq.gz	Fastqsanger.gz
	SRR22132726_2.fastq.gz	Fastqsanger.gz
	SRR22132727_1.fastq.gz	Fastqsanger.gz

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Effects of 17-DMAG treatment on transcription in 4T1 cells populations resistant and non-resistant to 17-DMAG

Project description:Activation of endogenous retrotransposons frequently occurs in cancer cells and contributes to tumor genomic instability. To test whether inhibition of retrotranspositions has an anticancer effect, we used treatment with the nucleoside reverse transcriptase inhibitor (NRTI) stavudine in mouse cancer models, MMTV-HER2/Neu and Th-MYCN, that spontaneously develop breast cancer and neuroblastoma, respectively. In both cases, stavudine in drinking water did not affect tumor incidence nor demonstrate any direct antitumor effects. However, stavudine dramatically extended progression-free survival in both models following an initial complete response to chemotherapy. To approach the mechanism underlying this phenomenon, we analyzed the effect of NRTI on the selection of treatment-resistant variants in tumor cells in culture. Cultivation of mouse breast carcinoma 4T1 in the presence of stavudine dramatically reduced the frequency of cells capable of surviving treatment with anticancer drugs. Global transcriptome analysis demonstrated that the acquisition of drug resistance by 4T1 cells was accompanied by an increase in the constitutive activity of interferon type I and NF-ϰB pathways and an elevated expression of LINE-1 elements, which are known to induce inflammatory responses via their products of reverse transcription. Treatment with NRTI reduced NF-ϰB activity and reverted drug resistance. Furthermore, the inducible expression of LINE-1 stimulated inflammatory response and increased the frequency of drug resistant variants in a tumor cell population. These results indicate a new mechanism by which retrotransposon desilencing can stimulate tumor cell survival during treatment and suggest reverse transcriptase inhibition as a potential new therapeutic approach for targeting the development of drug resistant cancers.

2022-11-04 | GSE217036 | GEO

17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Treating Patients With an Advanced Solid Tumor or Lymphoma

Project description:RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with an advanced solid tumor or lymphoma.

| 2011214 | ecrin-mdr-crc

17-DMAG treatment in primary CLL B cells

Project description:We used microarrays to analyze gene expression following treatment of leukemic B cells with the Hsp90 inhibitor 17-DMAG. Gene expression profiling reveals the role of SOCS3 in cytokine signaling in CLL Primary cells from CLL patients were isolated and treated in vitro with 17-DMAG. Cells were collected for viability, gene expression analysis and cell signaling and migration assays.

2016-07-01 | E-GEOD-76546 | biostudies-arrayexpress

17-DMAG treatment in primary CLL B cells

2016-07-01 | GSE76546 | GEO

Identification of 17-DMAG as a novel KDM4B inhibitor for combination therapy [RNA-seq]

Project description:Histone lysine demethylases (KDMs) are emerging as therapeutic targets in cancer. Development of potent KDM inhibitors may provide additional options for epigenomics-oriented therapies. Using a Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) functional demethylation assay, in combination with a high-content immunofluorescence imaging phenotypic screen, Matrix-Assisted Laser Desorption/Ionization- Fourier Transform Ion Cyclotron Resonance mass spectrometry (MALDI-FTICR MS) and Amplified Luminescent Proximity Homogeneous Assay (ALPHA), we identified geldanamycin, an inhibitor of heat shock protein 90 (Hsp90), as a novel inhibitor of JmjC-domain containing demethylases such as KDM4B. We further found that geldanamycin can destabilize the PAX3-FOXO1 fusion oncoprotein, an Hsp90 client, which is a driver of clinically unfavorable alveolar rhabdomyosarcoma (aRMS). We then hypothesized that dual inhibition of PAX3-FOXO1 and epigenetic modifiers of aRMS would have synergistic antitumor activity. We repurposed the geldanamycin analog 17-DMAG to target aRMS and found that 17-DMAG significantly delays tumor growth , extends survival in xenograft mouse models, and inhibits expression of PAX3-FOXO1 targets and multiple oncogenic pathways including MYC, E2F and NOTCH. In addition, the combination of 17-DMAG with conventional chemotherapy or the bromodomain inhibitor JQ1 significantly enhances therapeutic efficacy. In summary, we have identified geldanamycin and 17-DMAG as dual KDM/Hsp90 inhibitors and 17-DMAG is efficacious against PAX3-FOXO1-driven rhabdomyosarcoma.

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4T1 vs. MMP3-low 4T1

Project description:Molecular comparison between control 4T1 cells with MMP3-low 4T1 cells RNA extracted from biological triplicates of each of the above mentioned cell populations were subjected to microarray analysis

2015-04-22 | E-GEOD-68100 | biostudies-arrayexpress

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Project description:In this project, 4T1 parental cells (4T1/WT) were exposed to increasing concentrations of epirubicin (EPB) to establish a novel multi-drug resistant CSC-like breast cancer cell line (4T1/EPB). The ubiquitinated proteins were enriched from 4T1/WT or 4T1/EPB derived cell lysate using a-Al2O3-Vx3 nanoparticles to produce the covalently linked product UPs nanovaccine. Label-free LC-MS/MS mass spectrometry was used to detect the type and amount of enriched proteins of UPs from the 4T1/WT cells and the 4T1/EPB cells.

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Identification of 17-DMAG as a novel KDM4B inhibitor for combination therapy

Project description:Identification of 17-DMAG as a novel KDM4B inhibitor for combination therapy

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Identification of 17-DMAG as a novel KDM4B inhibitor for combination therapy [ChIP-seq]

Project description:Identification of 17-DMAG as a novel KDM4B inhibitor for combination therapy [ChIP-seq]

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