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IL-1β expression driven by androgen receptor absence or inactivation promotes prostate cancer bone metastasis

DiNatale, Anthony ; Worrede, Asurayya ; Iqbal, Waleed ; Marchioli, Michael ; Toth, Allison ; Sjöström, Martin LU ; Zhu, Xiaolin ; Corey, Eva ; Feng, Felix Y and Zhou, Wanding , et al. (2022) In Cancer Research Communications 2(12). p.1545-1557
Abstract

We report the inverse association between the expression of androgen receptor (AR) and interleukin-1beta (IL-1β) in a cohort of patients with metastatic castration resistant prostate cancer (mCRPC). We also discovered that AR represses the IL-1β gene by binding an androgen response element (ARE) half-site located within the promoter, which explains the IL-1β expression in AR-negative (ARNEG) cancer cells. Consistently, androgen-depletion or AR-pathway inhibitors (ARIs) de-repressed IL-1β in ARPOS cancer cells, both in vitro and in vivo. The AR transcriptional repression is sustained by histone de-acetylation at the H3K27 mark in the IL-1β promoter. Notably, patients' data suggest that DNA methylation prevents IL-1β expression, even if... (More)

We report the inverse association between the expression of androgen receptor (AR) and interleukin-1beta (IL-1β) in a cohort of patients with metastatic castration resistant prostate cancer (mCRPC). We also discovered that AR represses the IL-1β gene by binding an androgen response element (ARE) half-site located within the promoter, which explains the IL-1β expression in AR-negative (ARNEG) cancer cells. Consistently, androgen-depletion or AR-pathway inhibitors (ARIs) de-repressed IL-1β in ARPOS cancer cells, both in vitro and in vivo. The AR transcriptional repression is sustained by histone de-acetylation at the H3K27 mark in the IL-1β promoter. Notably, patients' data suggest that DNA methylation prevents IL-1β expression, even if the AR-signaling axis is inactive. Our previous studies show that secreted IL-1β supports metastatic progression in mice by altering the transcriptome of tumor-associated bone stroma. Thus, in prostate cancer patients harboring ARNEG tumor cells or treated with ADT/ARIs, and with the IL-1β gene unmethylated, IL-1β could condition the metastatic microenvironment to sustain disease progression.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Male, Animals, Mice, Receptors, Androgen/genetics, Interleukin-1beta/genetics, Androgens, Prostatic Neoplasms/genetics, Signal Transduction/genetics, Bone Neoplasms/genetics, Tumor Microenvironment
in
Cancer Research Communications
volume
2
issue
12
pages
1545 - 1557
external identifiers
  • pmid:36561929
  • scopus:85192635759
ISSN
2767-9764
DOI
10.1158/2767-9764.crc-22-0262
language
English
LU publication?
no
id
bf62f2d3-0f3a-4d87-b7bc-f0267654ee2d
date added to LUP
2026-02-20 13:46:33
date last changed
2026-02-21 04:02:09
@article{bf62f2d3-0f3a-4d87-b7bc-f0267654ee2d,
  abstract     = {{<p>We report the inverse association between the expression of androgen receptor (AR) and interleukin-1beta (IL-1β) in a cohort of patients with metastatic castration resistant prostate cancer (mCRPC). We also discovered that AR represses the IL-1β gene by binding an androgen response element (ARE) half-site located within the promoter, which explains the IL-1β expression in AR-negative (ARNEG) cancer cells. Consistently, androgen-depletion or AR-pathway inhibitors (ARIs) de-repressed IL-1β in ARPOS cancer cells, both in vitro and in vivo. The AR transcriptional repression is sustained by histone de-acetylation at the H3K27 mark in the IL-1β promoter. Notably, patients' data suggest that DNA methylation prevents IL-1β expression, even if the AR-signaling axis is inactive. Our previous studies show that secreted IL-1β supports metastatic progression in mice by altering the transcriptome of tumor-associated bone stroma. Thus, in prostate cancer patients harboring ARNEG tumor cells or treated with ADT/ARIs, and with the IL-1β gene unmethylated, IL-1β could condition the metastatic microenvironment to sustain disease progression.</p>}},
  author       = {{DiNatale, Anthony and Worrede, Asurayya and Iqbal, Waleed and Marchioli, Michael and Toth, Allison and Sjöström, Martin and Zhu, Xiaolin and Corey, Eva and Feng, Felix Y and Zhou, Wanding and Fatatis, Alessandro}},
  issn         = {{2767-9764}},
  keywords     = {{Humans; Male; Animals; Mice; Receptors, Androgen/genetics; Interleukin-1beta/genetics; Androgens; Prostatic Neoplasms/genetics; Signal Transduction/genetics; Bone Neoplasms/genetics; Tumor Microenvironment}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1545--1557}},
  series       = {{Cancer Research Communications}},
  title        = {{IL-1β expression driven by androgen receptor absence or inactivation promotes prostate cancer bone metastasis}},
  url          = {{http://dx.doi.org/10.1158/2767-9764.crc-22-0262}},
  doi          = {{10.1158/2767-9764.crc-22-0262}},
  volume       = {{2}},
  year         = {{2022}},
}