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| Status |
Public on May 30, 2013 |
| Title |
Glycosylation regulates the stability of c-MYC |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Tumorigenesis is characterised by changes in transcriptional regulation and the androgen receptor (AR) has been identified as a key driver in prostate cancer. In this study, we show that the hexosamine biosynthetic pathway (HBP) genes are overexpressed in clinical prostate cancer and androgen-regulated in cell-lines. HBP senses metabolic status of the cell and produces an essential substrate for O-GlcNAc transferase (OGT), which regulates target proteins via glycosylation. Using immunohistochemistry, we found that OGT is up-regulated in the protein level in prostate cancer (n=1987) and its expression correlates with high Gleason Score, pT and pN stages and biochemical recurrence (for all, p<0.0001). Both a small molecule inhibitor and siRNAs targeting OGT decreased prostate cancer cell growth. Microarray profiling revealed that the principal effects of the OGT inhibitor in prostate cancer cells are on cell cycle progression and DNA replication. We identified MYC as a candidate upstream regulator of these genes and found that OGT inhibitor caused a dose-dependent loss of c-MYC protein but not mRNA in cell lines. Finally, we observed a statistically significant co-expression between c-MYC and OGT in human prostate cancer samples (n=1306, p=0.0012).
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| Overall design |
Total RNA was extracted and experiment has three biological replicates for each condition, conditions are: 12 hours ST045849, 24 hours ST045849, 12 hours vehicle, 24 hours vehicle, 12 hours siOGT, 24 hours siOGT, 12 hours scrambled, 24 hours scrambled
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| Contributor(s) |
Itkonen HM, Minner S, Guldvik I, Sandman MJ, Tsourlakis MC, Berge V, Svinland A, Schlomm T, Mills IG |
| Citation(s) |
23720054 |
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| Submission date |
Feb 25, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Ian Mills |
| E-mail(s) |
ian.mills@ncmm.uio.no
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| Organization name |
University of Oslo
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| Department |
Centre for Molecular Medicine Norway
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| Lab |
Prostate Cancer Research Group
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| Street address |
Gaustadalleen 21
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| City |
Oslo |
| ZIP/Postal code |
0349 |
| Country |
Norway |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA190675 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44624_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE44624_non-normalized.txt.gz |
6.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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