The epigenetic function of androgen receptor in prostate cancer progression

Takahiro Sawada; Yoshiaki Kanemoto; Tomohiro Kurokawa; Shigeaki Kato

doi:10.3389/fcell.2023.1083486

The epigenetic function of androgen receptor in prostate cancer progression

Front Cell Dev Biol. 2023 Mar 21:11:1083486. doi: 10.3389/fcell.2023.1083486. eCollection 2023.

Authors

Takahiro Sawada^{1

2}, Yoshiaki Kanemoto^{1

2}, Tomohiro Kurokawa^{1

2

3}, Shigeaki Kato^{1

2

3}

Affiliations

¹ Graduate School of Life Science and Engineering, Iryo Sosei University, Fukushima, Japan.
² Research Institute of Innovative Medicine, Tokiwa Foundation, Fukushima, Japan.
³ School of Medicine, Fukushima Medical University, Fukushima, Japan.

Abstract

Androgen and androgen deprivation (castration) therapies, including androgen receptor antagonists, are clinically used to treat patients with prostate cancer. However, most hormone-dependent prostate cancer patients progress into a malignant state with loss of hormone-dependency, known as castration (drug)-resistant prostate cancer (CRPC), after prolong androgen-based treatments. Even in the CRPC state with irreversible malignancy, androgen receptor (AR) expression is detectable. An epigenetic transition to CRPC induced by the action of AR-mediated androgen could be speculated in the patients with prostate cancer. Androgen receptors belongs to the nuclear receptor superfamily with 48 members in humans, and acts as a ligand-dependent transcriptional factor, leading to local chromatin reorganization for ligand-dependent gene regulation. In this review, we discussed the transcriptional/epigenetic regulatory functions of AR, with emphasis on the clinical applications of AR ligands, AR protein co-regulators, and AR RNA coregulator (enhancer RNA), especially in chromatin reorganization, in patients with prostate cancer.

Keywords: androgens; chromatin reorganization; epigenetic; genome; prostate cancer.

Publication types

Review

Grants and funding

This study was financially supported by a grant from the Tokiwa Foundation (SK) and the practical development projects by Fukushima prefecture for the Research Institute of Innovative Medicine, Tokiwa Foundation.