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| Status |
Public on Dec 17, 2010 |
| Title |
Expression data from MTDH knockdown in the Hec50co endometrial cancer cell line |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| 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.
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| Overall design |
The microarray was performed on three biological triplicates as well as three experimental triplictes of stable knockdown and control cells. MTDH was knocked down using a shRNA.
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| Contributor(s) |
Meng X, Brachova P, Leslie K |
| Citation(s) |
21687633 |
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| Submission date |
Dec 17, 2010 |
| Last update date |
Jul 26, 2018 |
| Contact name |
xiangbing meng |
| E-mail(s) |
Xiangbing-meng@uiowa.edu
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| Organization name |
University of Iowa
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| Street address |
375 Newton Road
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| City |
Iowa City |
| State/province |
IA |
| ZIP/Postal code |
52242 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM641795 |
MTDH knockdown, biological replicate 1 |
| GSM641796 |
MTDH knockdown, biological replicate 2 |
| GSM641797 |
MTDH knockdown, biological replicate 3 |
| GSM641798 |
MTDH control, biological replicate 1 |
| GSM641799 |
MTDH control, biological replicate 2 |
| GSM641800 |
MTDH control, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA135381 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26134_RAW.tar |
24.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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