Role of Androgen Receptor in Progression of LNCaP Prostate Cancer Cells from G1 to S Phase

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Feb 26

PMID 23437213

Citations 18

Authors

Shalini Murthy

Min Wu

V Uma Bai

Zizheng Hou

Mani Menon

Evelyn R Barrack

Sahn-Ho Kim

G Prem-Veer Reddy

Affiliations

Soon will be listed here.

Abstract

Background: The androgen receptor (AR) plays a critical role in the proliferation of prostate cancer cells. However, its mechanism of action in proliferation remains unknown. An understanding of the mechanism of AR action in proliferation may lead to the development of effective strategies for the treatment of prostate cancer.

Methodology/principal Findings: In this study we report that pulse treatment of synchronized LNCaP cells with Casodex, an AR-antagonist, for 4 hours in mid-G(1) phase was sufficient to prevent cells from entering S phase. Since the assembly of pre-replication complex (pre-RC) in G(1) is required for the progression of cells from G(1) to S phase, the effect of Casodex during mid-G(1) suggested that the role of AR in proliferation might be to regulate the assembly of pre-RC. To test this possibility, we investigated the interaction between AR and Cdc6, an essential component of pre-RC in LNCaP cells. AR co-localized and co-immunoprecipitated with Cdc6, and Casodex treatment disrupted this interaction. AR-immunoprecipitate (AR-IP) also contained cyclin E and cyclin A, which play a critical role in pre-RC assembly and cell cycle entry into S phase, and DNA polymerase-α, PCNA, and ribonucleotide reductase, which are essential for the initiation of DNA synthesis. In addition, in cells in S phase, AR co-sedimented with components of the DNA replication machinery of cells that entered S phase.

Conclusions/significance: Together, these observations suggest a novel role of AR as a component of the pre-RC to exert control over progression of LNCaP cells from G(1) to S phase through a mechanism that is independent of its role as a transcription factor.

Citing Articles

Inhibition of -Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.

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Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Combination with Ralaniten Analogs for the Treatment of Androgen Receptor-positive Prostate and Breast Cancers.

Tien A, Sadar M Mol Cancer Ther. 2021; 21(2):294-309.

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Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.

Lu S, Dong Z Int J Oncol. 2021; 59(1).

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Identifying metastatic ability of prostate cancer cell lines using native fluorescence spectroscopy and machine learning methods.

Xue J, Pu Y, Smith J, Gao X, Wang C, Wu B Sci Rep. 2021; 11(1):2282.

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