Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA microarray analysis of global gene regulation by AdpAch in Streptomyces chattanoogensis

ABSTRACT: The effects of AdpAch on transcription of all protein-coding genes of S. griseus were evaluated by comparison of the transcriptomes of the wild-type to that of the ∆adpAch mutant strain We compared the pattern of gene expression of the wild-type (WT) to that of the ∆adpAch mutant strain. Mycelium was harvested after 16h, 24h, and 36h of growth and RNA was isolated from three independent cultures of each strain. For DNA microarray analysis of mutant strains, we considered a fold change of ≥2 and ≤0.5 of that of the WT strains, respectively, with a P-value <0.05 to be significant. According to these criteria, approximately 1400 genes were differentially expressed at all time points

ORGANISM(S): Streptomyces chattanoogensis

SUBMITTER: Pin Yu

PROVIDER: E-GEOD-59806 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.

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DNA microarray analysis of global gene regulation by AdpAch in Streptomyces chattanoogensis

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