The Role of Nuclear Receptors in Prostate Cancer.

Masaki Shiota,Naohiro Fujimoto,Masatoshi Eto,Eiji Kashiwagi

doi:10.3390/cells8060602

Masaki Shiota, Naohiro Fujimoto + Show 2 more

Open Access

https://doi.org/10.3390/cells8060602

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Abstract

The nuclear receptor (NR) superfamily consists of 48 members that are divided into seven subfamilies. NRs are transcription factors that play an important role in a number of biological processes. The NR superfamily includes androgen receptor, which is a key player in prostate cancer pathogenesis, suggesting the functional roles of other NRs in prostate cancer. The findings on the roles of NRs in prostate cancer thus far have shown that several NRs such as vitamin D receptor, estrogen receptor β, and mineralocorticoid receptor play antioncogenic roles, while other NRs such as peroxisome proliferator-activated receptor γ and estrogen receptor α as well as androgen receptor play oncogenic roles. However, the roles of other NRs in prostate cancer remain controversial or uninvestigated. Further research on the role of NRs in prostate cancer is required and may lead to the development of novel preventions and therapeutics for prostate cancer.

Highlights

Prostate cancer is primarily characterized by a dependence on the axis of androgen and its cognitive receptor, the nuclear receptor (NR) androgen receptor (AR), which plays roles in carcinogenesis, cancer development, disease progression, and treatment resistance [1]
This subfamily consists of the steroid receptors (SRs) including estrogen receptors (ERs), estrogen-related receptors (ERRs), AR, glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and progesterone receptor (PR) [3]
5 contains steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1), which are generally still classified as orphan receptors, but phospholipids were suggested as possible ligands

Summary

Introduction

Prostate cancer is primarily characterized by a dependence on the axis of androgen and its cognitive receptor, the nuclear receptor (NR) androgen receptor (AR), which plays roles in carcinogenesis, cancer development, disease progression, and treatment resistance [1]. NRs are transcription factors that play important functions in various biological processes including growth, development, metabolism, reproduction, and inflammation [3]. The expression levels of several NRs including LXRα, LXRβ, RARγ, and RXRα are downregulated in malignant-transformed prostate epithelial RWPE-2 cells as well as clinical prostate cancer samples [7]. These studies suggest that better clarification of the precise roles of NRs in prostate cancer may help better elucidate their cellular functions but may lead to the development of novel prevention and therapeutic strategies for prostate cancer. We summarize the roles of NRs in prostate cancer according to the classification into subfamilies with a focus on NRs other than AR (Table 1)

Subfamily 0

Subfamily 2

Subfamily 3

Subfamilies 5 and 6

Conclusions and Future Directions