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| Status |
Public on Jun 15, 2016 |
| Title |
Acquired resistance of Jurkat cells to TNF-related apoptosis-inducing ligand (TRAIL): a role for histone deacetylase inhibitors as powerful apoptosis sensitizer. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be a potent inducer of apoptosis in various cancer cell lines and primary cancer cells. However, in clinical trials administration of recombinant TRAIL or TRAIL death receptor agonists did not show sufficient efficacy for treatment of tested malignant disorders compared to standard chemotherapy. Acquired resistance of cancer cells to TRAIL and to other “death receptor” ligands may explain not only the inability of TRAIL and TRAIL “death receptor” agonists to achieve the clearance of cancer cells in vivo but also the escape of cancer cells from immune cell – mediated killing. Selective pressure of TRAIL on TRAIL-sensitive Jurkat T-lymphoblastic leukemia cells provided several TRAIL resistant Jurkat cell line clones (TR1, TR2, TR3). Irrespective of molecular changes histone deacetylase inhibitors (HDACi), such as suberoylanilide-hydroxamic acid (SAHA, vorinostat), were able to restore sensitivity of all three TRAIL-resistant clones to TRAIL. Gene expression analysis of TR1 clone treated with SAHA 1microM for 12 hours compared to untreated TR1 clone showed significant decrease in expression of CFLAR/cFLIP (0.71; p=0.006), BIRC5/survivin (0.80; p=0.024) and BID (0.66; p<0.001). Expression of both TRAIL “death” receptors DR4 (1.57; p<0.001) and DR5 (1.47; p=0.002) were significantly increased compared to untreated TR1 cells. The mRNA expression of caspases-2,-3,-8,-9,-10 did not significantly change with the SAHA treatment.
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| Overall design |
Total cellular RNA was isolated from biologic duplicates of untreated Jurkat cells (WT), TRAIL resistant Jurkat cell clone (TR1) and 1 µM and 0.5 µM suberoylanilide-hydroxamic acid (SAHA, vorinostat) treated TR1 cell clones for 12 hours. Jurkat cell line subclones TR1was established by selective pressure of TRAIL 1000 ng/mL on Jurkat cells over the period of 12 weeks.
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| Contributor(s) |
Klener P, Ivanek R, Zivny J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jun 15, 2012 |
| Last update date |
Jun 15, 2016 |
| Contact name |
Robert Ivanek |
| Phone |
+41 61 207 35 41
|
| Organization name |
University of Basel
|
| Department |
Department of Biomedicine
|
| Lab |
Bioinformatics
|
| Street address |
Hebelstrasse 20
|
| City |
Basel |
| ZIP/Postal code |
4053 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
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| Samples (8)
|
| GSM948963 |
Jurkat_TRAIL_resistant_clone1_untreated_rep2 |
| GSM948964 |
Jurkat_TRAIL_resistant_clone1_0.5microM_SAHA_rep1 |
| GSM948965 |
Jurkat_TRAIL_resistant_clone1_0.5microM_SAHA_rep2 |
| GSM948966 |
Jurkat_TRAIL_resistant_clone1_1microM_SAHA_rep1 |
| GSM948967 |
Jurkat_TRAIL_resistant_clone1_1microM_SAHA_rep2 |
|
| Relations |
| BioProject |
PRJNA168558 |
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