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Series GSE27828 Query DataSets for GSE27828
Status Public on May 01, 2011
Title Expression data from metadherin (MTDH) knockdown in the Ishikawa H endometrial cancer cell line
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH has recently been implicated in poor clinical outcome in breast cancer, neroblastoma, hepatocellular carcinoma and prostate cancer. In this present study, we focused on the therapeutic benefit of MTDH depletion to restore sensitivity to cell death mediated by a combinatorial therapy of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which promotes death of cancerous cells of the human reproductive tract, and histone deacetylase (HDAC) inhibitors, which have been shown to increase sensitivity of cancer cells to TRAIL-induced apoptosis. Our data indicate that depletion of MTDH in endometrial cancer cells results in sensitization of cells that were previously resistant to cell death mediated by combinatorial treatment with TRAIL and HDAC inhibitor LBH589. MTDH was found to be involved in G2/M checkpoint regulation in response to LBH589 alone or LBH589 in combination with TRAIL, suggesting that MTDH functions at the cell cycle checkpoint to accomplish resistance.Using microarray technology, we identified 57 downstream target genes of MTDH, including Calbindin 1 and Galectin 1, which may contribute to MTDH-mediated resistance to combinatorial TRAIL and HDAC inhibitor targeted therapy. Inhibition of PDK1,AKT phosphorylation and increase Bim expression and XIAP degradation may result in sensitivity to cell death induction in MTDH depleted Hec50co cells by TRAIL and LBH 589 combination treatment. These findings indicate that depletion of MTDH is a potentially novel avenue for effective cancer therapy.
 
Overall design The microarray was performed on three biological triplicates as well as three experimental triplicates of stable knockdown and control cells. MTDH was knocked down using a shRNA.
 
Contributor(s) Meng X, Brachova P, Leslie K
Citation(s) 21687633
Submission date Mar 08, 2011
Last update date Feb 18, 2019
Contact name xiangbing meng
E-mail(s) Xiangbing-meng@uiowa.edu
Organization name University of Iowa
Street address 375 Newton Road
City Iowa City
State/province IA
ZIP/Postal code 52242
Country USA
 
Platforms (1)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
Samples (6)
GSM687005 MTDH control, biological replicate 1
GSM687006 MTDH control, biological replicate 2
GSM687007 MTDH control, biological replicate 3
Relations
BioProject PRJNA137889

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Supplementary file Size Download File type/resource
GSE27828_RAW.tar 123.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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