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| Status |
Public on Jul 09, 2024 |
| Title |
Different doses of androgens induce the expression of distinct gene expression programs [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Most prostate cancers express the androgen receptor (AR), and tumor growth and progression are facilitated by exceptionally low levels of systemic or intratumorally produced androgens. Paradoxically, high dose androgens have also shown considerable efficacy in the treatment of patients with late-stage metastatic PCa. In probing the mechanisms that enable cells to recognize and respond to different levels of the same hormone, it was determined that low levels of androgens, functioning through an AR monomer, facilitates a non-genomic activation of the mTOR signaling pathway to drive proliferation. Conversely, high dose androgens facilitate the formation of AR dimers to suppress c-MYC expression, inhibit proliferation and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR action in PCa and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies.
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| Overall design |
To identify AR directly regulated enhancers responsible for the non-linear proliferative responses to androgens, we performed an unbiased genome wide ChIP-sequencing study in both VCaP and LNCaP cells. VCaP and LNCaP cells where treated with either vehicle, or increasing concentrations of low-dose 0.01, 0.03, 0.06, 0.1 nM R1881) or High-Dose (10nM R1881) androgens for 24 hrs.
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| Contributor(s) |
Safi R, Watkinson P, Qin X, Lee M, Blattler A, Fontanillo C, Owzar K, Norris JD, McDonnell DP |
| Citation(s) |
39227594 |
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| Submission date |
Mar 28, 2024 |
| Last update date |
Oct 01, 2024 |
| Contact name |
Xiaodi Qin |
| Organization name |
Duke Cancer Institute
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| Street address |
2424 Erwin Road
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| City |
Durham |
| ZIP/Postal code |
27705 |
| Country |
USA |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (40)
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| GSM8177980 |
LNCaP, R1881, 0.03 nM, 24 hours, AR, Rep1 |
| GSM8177981 |
LNCaP, R1881, 0.03 nM, 24 hours, AR, Rep2 |
| GSM8177982 |
LNCaP, R1881, 0.03 nM, 24 hours, Input, Rep1 |
| GSM8177983 |
LNCaP, R1881, 0.03 nM, 24 hours, Input, Rep2 |
| GSM8177984 |
LNCaP, R1881, 0.06 nM, 24 hours, AR, Rep1 |
| GSM8177985 |
LNCaP, R1881, 0.06 nM, 24 hours, AR, Rep2 |
| GSM8177986 |
LNCaP, R1881, 0.06 nM, 24 hours, Input, Rep1 |
| GSM8177987 |
LNCaP, R1881, 0.06 nM, 24 hours, Input, Rep2 |
| GSM8177988 |
LNCaP, R1881, 0.1 nM, 24 hours, AR, Rep1 |
| GSM8177989 |
LNCaP, R1881, 0.1 nM, 24 hours, AR, Rep2 |
| GSM8177990 |
LNCaP, R1881, 0.1 nM, 24 hours, Input, Rep1 |
| GSM8177991 |
LNCaP, R1881, 0.1 nM, 24 hours, Input, Rep2 |
| GSM8177992 |
LNCaP, R1881, 10 nM, 24 hours, AR, Rep1 |
| GSM8177993 |
LNCaP, R1881, 10 nM, 24 hours, AR, Rep2 |
| GSM8177994 |
LNCaP, R1881, 10 nM, 24 hours, Input, Rep1 |
| GSM8177995 |
LNCaP, R1881, 10 nM, 24 hours, Input, Rep2 |
| GSM8177996 |
LNCaP, Vehicle_CFS, 0, 24 hours, AR, Rep1 |
| GSM8177997 |
LNCaP, Vehicle_CFS, 0, 24 hours, AR, Rep2 |
| GSM8177998 |
LNCaP, Vehicle_CFS, 0, 24 hours, Input, Rep1 |
| GSM8177999 |
LNCaP, Vehicle_CFS, 0, 24 hours, Input, Rep2 |
| GSM8178000 |
VCaP, R1881, 0.01 nM, 24 hours, AR, Rep1 |
| GSM8178001 |
VCaP, R1881, 0.01 nM, 24 hours, AR, Rep2 |
| GSM8178002 |
VCaP, R1881, 0.01 nM, 24 hours, Input, Rep1 |
| GSM8178003 |
VCaP, R1881, 0.01 nM, 24 hours, Input, Rep2 |
| GSM8178004 |
VCaP, R1881, 0.03 nM, 24 hours, AR, Rep1 |
| GSM8178005 |
VCaP, R1881, 0.03 nM, 24 hours, AR, Rep2 |
| GSM8178006 |
VCaP, R1881, 0.03 nM, 24 hours, Input, Rep1 |
| GSM8178007 |
VCaP, R1881, 0.03 nM, 24 hours, Input, Rep2 |
| GSM8178008 |
VCaP, R1881, 0.06 nM, 24 hours, AR, Rep1 |
| GSM8178009 |
VCaP, R1881, 0.06 nM, 24 hours, AR, Rep2 |
| GSM8178010 |
VCaP, R1881, 0.06 nM, 24 hours, Input, Rep1 |
| GSM8178011 |
VCaP, R1881, 0.06 nM, 24 hours, Input, Rep2 |
| GSM8178012 |
VCaP, R1881, 10 nM, 24 hours, AR, Rep1 |
| GSM8178013 |
VCaP, R1881, 10 nM, 24 hours, AR, Rep2 |
| GSM8178014 |
VCaP, R1881, 10 nM, 24 hours, Input, Rep1 |
| GSM8178015 |
VCaP, R1881, 10 nM, 24 hours, Input, Rep2 |
| GSM8178016 |
VCaP, Vehicle_CFS, 0, 24 hours, AR, Rep1 |
| GSM8178017 |
VCaP, Vehicle_CFS, 0, 24 hours, AR, Rep2 |
| GSM8178018 |
VCaP, Vehicle_CFS, 0, 24 hours, Input, Rep1 |
| GSM8178019 |
VCaP, Vehicle_CFS, 0, 24 hours, Input, Rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE247593 |
Different doses of androgens induce the expression of distinct gene expression programs |
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| Relations |
| BioProject |
PRJNA1093098 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262744_RAW.tar |
15.5 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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