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Expression data analyzed with LPIA in A549 lung carcinoma cells treated with geldanamycin.

ABSTRACT: The statsitcal model, latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signﬁcant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26525 | GEO | 2011/01/11

SECONDARY ACCESSION(S): PRJNA136639

REPOSITORIES: GEO

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Expression data analyzed with LPIA in A549 lung carcinoma cells treated with geldanamycin.

Project description:The statsitcal model, latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signï¬cant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level. A549 lung carcinoma cells were allowed to adhere for 24h and further incubated in the presence of geldanamycin at a concentration equivalent to the determined IC50 of 40 nM or IC20 of 10 nM, or with vehicle DMSO (final concentration 0.4%). After 24h and 48 h, cells were harvested and total RNA was purified and processed for Affymetrix HG_U133_Plus_2.0 microarray analysis. Raw probe intensities were RMA-normalized and avereaged for three replicates for each condition. Probe sets for 54,120-annotated open reading frames were included in LPIA analysis.

2011-01-11 | E-GEOD-26525 | biostudies-arrayexpress

Transcription profiling of Arabidopsis plants after heat shock or treatment with HSP90 inhibitors (geldanamycin and radicicol)

Project description:Effect of heat shock or HSP90 inhibitors (geldanamycin and radicicol) on wild type Arabidopsis thaliana.

2007-06-01 | E-ATMX-12 | biostudies-arrayexpress

Transcriptome of the geldanamycin producer Streptomyces hygroscopicus XM201

Project description:For systematically improving geldanamycin yield, we investigated the gene expression profile on the fourth day during geldanamycin fermentation (geldanamycin began to largely accumulated on this day). According to the RNA-seq data, we deduced that the PKS genes gdmAI-AIII are rate-limiting genes for geldanamycin biosynthesis. We also found a strong endogeneous promoter according to the RNA-seq data and the reporter gene. Replacing the native PKS promoter with this strong promoter brought an obvious increase in geldanamycin yield.

2017-03-03 | GSE92334 | GEO

Response of Blastocladiella emersonii to hypoxia, iron deprivation and geldanamycin treatment followed by hypoxia.

Project description:Due to its aquatic saprophytic lifestyle, the fungus Blastocladiella emersonii seems to be adapted to low aerated environments and thus can be an interesting model of study of the hypoxic stress response. Iron deprivation, a hypoxia-mimicking stimulus due to HIF-1 stabilization, and geldanamycin, that causes HIF-1 depletion by HSP90 inhibition, are helpful parameters to find an evidence of an oxygen-dependent regulatory mechanism in B. emersonii similar to the metazoan HIF-1 pathway. Direct transcript comparison between cells grown under normoxic conditions (70%sat. O2 in air) and cells submitted to oxygen deprivation (direct and gradual) and iron (II) deprivation. It was also compared transcripts of cells submitted to direct 1-hour hypoxia (1%sat. O2) with cells treated with geldanamycin for 1 hour, followed to 1-hour hypoxia (1%sat. O2). There are at least 3 biological replicates (independent harvest) and 2 technical replicates of each array (L - left and R - right).

2010-06-24 | E-GEOD-17524 | biostudies-arrayexpress

Response of Blastocladiella emersonii to hypoxia, iron deprivation and geldanamycin treatment followed by hypoxia.

2009-08-07 | GSE17524 | GEO

Transcription profiling of wild type and delta-sba1 yeast treated with radicicol to study gene regulation by sba1

Project description:We wanted to study regulation of gene regulation by sba1 (ortholog of mammalian p23) in yeast. sba1/p23 binds to Hsp90 and acts as a co-chaperone. We have a small molecule, radicicol, an analog of geldanamycin to inhibit the binding of p23 to Hsp90. Consequently, we have analyzed the gene expression profile in 4 conditions, wt, delta-sba1; and when Hsp90 function is impaired, that is, wt and delta-sba1 treated with radicicol.

2009-10-14 | E-TABM-573 | biostudies-arrayexpress

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.

2020-12-21 | GSE151514 | GEO

Bioligical pathways of Hsp90 inhibitors in adult T cell leukemia cell lines

Project description:Heat shock protein 90 (Hsp90) is essential for the stability and the function of many client proteins, such as ERB2, C-RAF, CDK4, HIF-1 aplha and AKT. Recent reports demonstrated that inhibition of Hsp90 modulates multiple functions required for survival of human cancer, such as myeloma (Mitsiades et al, Blood:107, 1092, 2006), The aim of this study is evaluate the effect of Hsp90 inhibition, and to identify molecular pathways responsible for anti-proliferative effect on ATL cells. For Hsp90 inhibition, Geldanamycin derivates, 17AAG (17-allylamino -17-demethoxygeldanamycin) and 17DMAG (17-(dimethylaminoethylamino) 17-demethoxygeldanamycin) were used in this study. Interleukin 2-independent ATL cell lines (MT-2 and MT-4) and an interleukin 2-dependent ATL cell line (TaY-E10) were incubated, with or without Hsp90 inhibitors.

2009-05-27 | GSE12287 | GEO

Transcription profiling of human adult T cell leukemia cell lines to investigate the biological pathways of Hsp90 inhibitors

2009-06-08 | E-GEOD-12287 | biostudies-arrayexpress

Gene expression data from T cells and NK cells with and without treatment with Hsp90 inhibitor (Geldanamycin)

Project description:Hsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells. Analysis of human T cells (CD4, CD8) and NK cells treated with Hsp90 inhibitor.

2012-11-14 | E-GEOD-42253 | biostudies-arrayexpress

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