Androgen receptor coactivator p120 subtype β is highly expressed in prostate cancer

Muramatsu, Kazumichi; Matsui, Hiroshi; Sekine, Yoshitaka; Koike, Hidekazu; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

doi:10.12954/pi.12004

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…Once inside the nucleus, AR dimerizes and binds to its DNA binding element (ARE) and augments the transcription of multiple genes that are necessary for PCa survival, growth and invasion [55][56][57] . Many of the currently available antiandrogens attenuate AR signaling by competing with androgens for AR binding [58] and may also be effective in suppressing the recruitment of coactivators or by activating corepressors [59][60][61] . Therefore, in androgen-dependent PCa cells, ligand-mediated activation of AR can be downregulated by multiple hormone deprivation strategies that are implemented during ADT [62] and their biochemical failure enables tumor recurrence and distant metastasis [63] .…”

Section: Ar Signaling Hormone Deprivation and Crpc Outgrowthmentioning

confidence: 99%

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

Mondal¹,

Narwani²,

Notta³

et al. 2020

CDR

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Androgen deprivation therapy (ADT) is the mainstay regimen in patients with androgen-dependent prostate cancer (PCa). However, the selection of androgen-independent cancer cells leads to castrate resistant prostate cancer (CRPC). The aggressive phenotype of CRPC cells underscores the need to elucidate mechanisms and therapeutic strategies to suppress CRPC outgrowth. Despite ADT, the activation of androgen receptor (AR) transcription factor continues via crosstalk with parallel signaling pathways. Understanding of how these signaling cascades are initiated and amplified post-ADT is lacking. Hormone deprivation can increase oxidative stress and the resultant reactive oxygen species (ROS) may activate both AR and non-AR signaling. Moreover, ROS-induced inflammatory cytokines may further amplify these redox signaling pathways to augment AR function. However, clinical trials using ROS quenching small molecule antioxidants have not suppressed CRPC progression, suggesting that more potent and persistent suppression of redox signaling in CRPC cells will be needed. The transcription factor Nrf2 increases the expression of numerous antioxidant enzymes and downregulates the function of inflammatory transcription factors, e.g., nuclear factor kappa B. We documented that Nrf2 overexpression can suppress AR-mediated transcription in CRPC cell lines. Furthermore, two Nrf2 activating agents, sulforaphane (a phytochemical) and bardoxolone-methyl (a drug in clinical trial) suppress AR levels and sensitize CRPC cells to anti-androgens. These observations implicate the benefits of potent Nrf2-activators to suppress the lethal signaling cascades that lead to CRPC outgrowth. This review article will address the redox signaling networks that augment AR signaling during PCa progression to CRPC, and the possible utility of Nrf2-activating agents as an adjunct to ADT.

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Section: Ar Signaling Hormone Deprivation and Crpc Outgrowthmentioning

confidence: 99%

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

Mondal¹,

Narwani²,

Notta³

et al. 2020

CDR

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MiR-185 attenuates androgen receptor function in prostate cancer indirectly by targeting bromodomain containing 8 isoform 2, an androgen receptor co-activator

Jiang

Ruan

Wang

et al. 2016

Molecular and Cellular Endocrinology

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Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells

Iwanaga

Kawamura

Kubo

et al. 2022

Journal of Radiation Research

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Castration-resistant prostate cancer shows resistance to not only androgen deprivation therapy (ADT) but also X-ray therapy. On the other hand, carbon ion beams have a high biological effect and are used for various cancers showing resistance to X-ray therapy. The purposes of this study are to clarify the difference in the sensitivity of Castration-resistant prostate cancer to X-ray and carbon ion beams and to elucidate the mechanism. The androgen-insensitive prostate cancer cell line LNCaP-LA established by culturing the androgen-sensitive prostate cancer cell line LNCaP for 2 years in androgen-free medium was used for this study. First, colony formation assays were performed to investigate its sensitivity to X-ray and carbon ion beams. Next, DNA mutation analysis on 409 cancer-related genes and comprehensive transcriptome analysis (RNA-seq) were performed with a next-generation sequencer. Lethal dose 50 values of X-rays for LNCaP and LNCaP-LA were 1.4 Gy and 2.8 Gy, respectively (P < 0.01). The Lethal dose 50 values of carbon ion beams were 0.9 Gy and 0.7 Gy, respectively (P = 0.09). On DNA mutation analysis, AR mutation was observed specifically in LNCaP-LA. From RNA-seq, 181 genes were identified as differentially expressed genes (DEGs; FDR <0.10, P < 0.00076) between LNCaP and LNCaP-LA. Function analysis suggested that cell death was suppressed in LNCaP-LA, and pathway analysis suggested that the NRF2-pathway involved in intracellular oxidative stress prevention was activated in LNCaP-LA. LNCaP-LA showed X-ray resistance compared to LNCaP and sensitivity to carbon ion beams. The AR mutation and the NRF2-pathway were suggested as causes of resistance.

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Androgen receptor coactivator p120 subtype β is highly expressed in prostate cancer

Cited by 3 publications

References 15 publications

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

MiR-185 attenuates androgen receptor function in prostate cancer indirectly by targeting bromodomain containing 8 isoform 2, an androgen receptor co-activator

Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells

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