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| Status |
Public on Dec 18, 2009 |
| Title |
Time course of 1,25(OH)2D treated RWPE1 cells. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1α,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.
Results: We examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n=4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60 % up), 48 h, 3566 (38 % up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways). There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h.
Conclusions: Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.
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| Overall design |
RWPE1 cells were treated with medium containing 100 nM of 1,25(OH)2D or vehicle (0.1% ethanol) for 6, 24 or 48 hours (n=4 per treatment, 24 total samples). The transcripts levels in each sample were measured by using the Affymetrix HU133 plus 2.0 GeneChip (Affymetrix, Santa Clara, CA).
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| Contributor(s) |
Fleet JC, Kovalenko PL, Clinton SS |
| Citation(s) |
20070897 |
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| Submission date |
May 04, 2009 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Pavlo Kovalenko |
| E-mail(s) |
pkovalen@purdue.edu
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| Organization name |
Purdue University
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| Department |
Foods and Nutrition
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| Street address |
700 W State st
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| City |
West Lafayette |
| State/province |
IN |
| ZIP/Postal code |
47906 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (24)
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| GSM400051 |
RWPE1 cells, vehicle, 6h, biological rep1 |
| GSM400052 |
RWPE1 cells, vehicle, 6h, biological rep2 |
| GSM400053 |
RWPE1 cells, vehicle, 6h, biological rep3 |
| GSM400054 |
RWPE1 cells, vehicle, 6h, biological rep4 |
| GSM400055 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 6h, biological rep1 |
| GSM400056 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 6h, biological rep2 |
| GSM400057 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 6h, biological rep3 |
| GSM400058 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 6h, biological rep4 |
| GSM400059 |
RWPE1 cells, vehicle, 24h, biological rep1 |
| GSM400060 |
RWPE1 cells, vehicle, 24h, biological rep2 |
| GSM400061 |
RWPE1 cells, vehicle, 24h, biological rep3 |
| GSM400062 |
RWPE1 cells, vehicle, 24h, biological rep4 |
| GSM400063 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 24h, biological rep1 |
| GSM400064 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 24h, biological rep2 |
| GSM400065 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 24h, biological rep3 |
| GSM400066 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 24h, biological rep4 |
| GSM400067 |
RWPE1 cells, vehicle, 48h, biological rep1 |
| GSM400068 |
RWPE1 cells, vehicle, 48h, biological rep2 |
| GSM400069 |
RWPE1 cells, vehicle, 48h, biological rep3 |
| GSM400070 |
RWPE1 cells, vehicle, 48h, biological rep4 |
| GSM400071 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 48h, biological rep1 |
| GSM400072 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 48h, biological rep2 |
| GSM400073 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 48h, biological rep3 |
| GSM400074 |
RWPE1 cells, 100 nM of 1,25(OH)2D, 48h, biological rep4 |
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| Relations |
| BioProject |
PRJNA117003 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15947_RAW.tar |
115.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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