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| Status |
Public on Feb 01, 2018 |
| Title |
Identification of an IL-1-induced gene expression pattern in AR+ PCa cells that mimics the molecular phenotype of AR- PCa cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable; suggesting that IL-1 may also contribute to AR-targeted therapy resistance. Furthermore, IL-1 and AR protein levels negatively correlate in PCa tumor cells. Taken together, we hypothesize that IL-1 reprograms AR positive (AR+) PCa cells into AR negative (AR-) PCa cells that co-opt IL-1 signaling to ensure AR-independent survival in the inflammatory tumor microenvironment. Thus, we employed RNA sequencing to identify pathways that are modulated by IL-1 concomitant with IL-1-induced AR repression in PCa cells. Comparative analysis of sequencing data from the AR+ LNCaP PCa cell line versus the AR- PC3 PCa cell line reveals an IL-1-conferred gene suite in LNCaP cells that is constitutive in PC3 cells, and includes AR and AR target gene repression and the induction of prosurvival, lineage, and cancer stem cell genes. Bioinformatics analysis of the IL-1 regulated gene suite revealed that inflammatory and immune response pathways are primarily elicited; likely facilitating PCa cell survival in an inflammatory tumor microenvironment. Our data supports that IL-1 reprograms AR+ PCa cells to mimic AR- PCa gene expression patterns that favor AR-targeted treatment resistance and cell survival.
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| Overall design |
PCa cells were treated with vehicle control or IL-1β or grown in bone marrow stromal cell CM (conditioned media) from HS-5 bone marrow stromal cell lines for 3 days. At Day 3 RNA was extracted from 3 biological replicates for RNA-sequencing and confirmation analyses were performed using western blot and RT-QPCR.
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| Contributor(s) |
Thomas-Jardin S, Kanchwala M, Jacob J, Merchant S, Meade R, Gahnim N, Nawas A, Xing C, Delk N |
| Citation(s) |
29527701, 31959131, 34988553 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K01 CA160602 |
Cryptoprotective Autophagy in Bone Metastatic Prostate Cancer |
THE UNIVERSITY OF TEXAS AT DALLAS |
NIKKI A DELK |
| R21 CA175798 |
Role of Androgen Receptor in Bone Metastatic Prostate Cancer Apoptosis and NED |
THE UNIVERSITY OF TEXAS AT DALLAS |
NIKKI A DELK |
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| Submission date |
Oct 17, 2017 |
| Last update date |
Jan 11, 2022 |
| Contact name |
Nikki Delk |
| E-mail(s) |
nad140230@utdallas.edu
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| Phone |
9728832581
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| Organization name |
University of Texas at Dallas
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| Department |
Biological Sciences
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| Street address |
800 West Campbell Road
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| City |
Richardson |
| ZIP/Postal code |
75080 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| GSM2817826 |
LnCAP 25 ng/ml IL-1β, 1 |
| GSM2817827 |
LnCAP 25 ng/ml IL-1β, 2 |
| GSM2817828 |
LnCAP 25 ng/ml IL-1β, 3 |
| GSM2817829 |
PC3 PBS (Vehicle control), 1 |
| GSM2817830 |
PC3 PBS (Vehicle control), 2 |
| GSM2817831 |
PC3 PBS (Vehicle control), 3 |
| GSM2817832 |
LNCaP CM (control), 1 |
| GSM2817833 |
LNCaP CM (control), 2 |
| GSM2817834 |
LNCaP CM (control), 3 |
| GSM2817835 |
LNCaP HS-5 CM, 1 |
| GSM2817836 |
LNCaP HS-5 CM, 2 |
| GSM2817837 |
LNCaP HS-5 CM, 3 |
| GSM2817838 |
PC3 CM (control), 1 |
| GSM2817839 |
PC3 CM (control), 2 |
| GSM2817840 |
PC3 CM (control), 3 |
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| Relations |
| BioProject |
PRJNA414614 |
| SRA |
SRP120165 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE105088_GENES.feature_counts.tab.gz |
2.6 Mb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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