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| Status |
Public on Sep 30, 2018 |
| Title |
Genomic Analysis of DNA Repair Genes and Androgen Signaling in Prostate Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abstract Background. The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has important translational implications. Methods. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription. Results. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells. Conclusions. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer.
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| Overall design |
RNA was extracted from PC3-AR, VCaP, and LNCaP cells under untreated and androgen (2 nM, R1881) treated conditions. A total of 21 samples were sequenced with 3 replicates for each condition.
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| Contributor(s) |
Jividen K, Ratan A, Paschal BM |
| Citation(s) |
30305041, 33976187 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA214872 |
Parp Function in Prostate Cancer |
UNIVERSITY OF VIRGINIA CHARLOTTESVILLE |
BRYCE PASCHAL |
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| Submission date |
Sep 29, 2018 |
| Last update date |
May 20, 2021 |
| Contact name |
Aakrosh Ratan |
| Organization name |
University of Virginia
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| Department |
Center for Public Health Genomics
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| Street address |
1335 Lee Street, West Complex
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22903 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (21)
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| GSM3407118 |
PC3-AR_6hr_R1881, rep 1 |
| GSM3407119 |
PC3-AR_6hr_R1881, rep 2 |
| GSM3407120 |
PC3-AR_6hr_R1881, rep 3 |
| GSM3407121 |
PC3-AR_12hr_R1881, rep 1 |
| GSM3407122 |
PC3-AR_12hr_R1881, rep 2 |
| GSM3407123 |
PC3-AR_12hr_R1881, rep 3 |
| GSM3407124 |
VCaP_unt, rep 1 |
| GSM3407125 |
VCaP_unt, rep 2 |
| GSM3407126 |
VCaP_unt, rep 3 |
| GSM3407127 |
VCaP_24hr_R1881, rep 1 |
| GSM3407128 |
VCaP_24hr_R1881, rep 2 |
| GSM3407129 |
VCaP_24hr_R1881, rep 3 |
| GSM3407130 |
LNCaP_unt, rep 1 |
| GSM3407131 |
LNCaP_unt, rep 2 |
| GSM3407132 |
LNCaP_unt, rep 3 |
| GSM3407133 |
LNCaP_24hr_R1881, rep 1 |
| GSM3407134 |
LNCaP_24hr_R1881, rep 2 |
| GSM3407135 |
LNCaP_24hr_R1881, rep 3 |
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| Relations |
| BioProject |
PRJNA493954 |
| SRA |
SRP162931 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120660_PCamerge_hg38.csv.gz |
995.7 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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