Abstract
The androgen receptor (AR) plays a critical role in proliferation and viability of prostate cancer cells. Therefore, suppressing AR activity by androgen deprivation or anti-androgen treatment has been the frontline therapy for over six decades. However, these treatment strategies are not curative and patients succumb to castration-resistant disease. Although AR is evidently critical for proliferation of prostate cancer cells, very little is known about its mechanism of action in this process. Over the years, the role of AR in prostate cancer cell proliferation and viability has been studied by focusing primarily on its role as a transcription factor. However, recent observations indicate that besides its role as a transcription factor, AR interacts physically with components of the pre-replication complex (pre-RC) and DNA replication machinery (replitase). These interactions may enable AR to exert control over the process of DNA synthesis. In addition, alterations in the proteins that interact with AR in complexes required for DNA synthesis could lead to the development of hormone-refractory prostate cancer. These observations suggest a paradigm shift for the role of AR in proliferation of prostate cancer cells from its role as a transcription factor to a non-transcriptional role as a component of the replication machinery, interacting with cell cycle regulatory proteins and enzymes of DNA synthesis. We propose that a detailed understanding of the structural interactions between AR and the components of pre-RC and replitase may lead to the development of new strategies for the treatment of prostate cancer.
Keywords: Androgen Receptor, Cell Cycle, Pre-Replication Complex, DNA Replication, Prostate Cancer
Current Protein & Peptide Science
Title: Role of Androgen Receptor in Prostate Cancer Cell Cycle Regulation: Interaction with Cell Cycle Regulatory Proteins and Enzymes of DNA Synthesis
Volume: 11 Issue: 6
Author(s): Arun Sivanandam, Shalini Murthy, Sahn-Ho Kim, Evelyn R. Barrack and G. Prem Veer Reddy
Affiliation:
Keywords: Androgen Receptor, Cell Cycle, Pre-Replication Complex, DNA Replication, Prostate Cancer
Abstract: The androgen receptor (AR) plays a critical role in proliferation and viability of prostate cancer cells. Therefore, suppressing AR activity by androgen deprivation or anti-androgen treatment has been the frontline therapy for over six decades. However, these treatment strategies are not curative and patients succumb to castration-resistant disease. Although AR is evidently critical for proliferation of prostate cancer cells, very little is known about its mechanism of action in this process. Over the years, the role of AR in prostate cancer cell proliferation and viability has been studied by focusing primarily on its role as a transcription factor. However, recent observations indicate that besides its role as a transcription factor, AR interacts physically with components of the pre-replication complex (pre-RC) and DNA replication machinery (replitase). These interactions may enable AR to exert control over the process of DNA synthesis. In addition, alterations in the proteins that interact with AR in complexes required for DNA synthesis could lead to the development of hormone-refractory prostate cancer. These observations suggest a paradigm shift for the role of AR in proliferation of prostate cancer cells from its role as a transcription factor to a non-transcriptional role as a component of the replication machinery, interacting with cell cycle regulatory proteins and enzymes of DNA synthesis. We propose that a detailed understanding of the structural interactions between AR and the components of pre-RC and replitase may lead to the development of new strategies for the treatment of prostate cancer.
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Cite this article as:
Sivanandam Arun, Murthy Shalini, Kim Sahn-Ho, R. Barrack Evelyn and Prem Veer Reddy G., Role of Androgen Receptor in Prostate Cancer Cell Cycle Regulation: Interaction with Cell Cycle Regulatory Proteins and Enzymes of DNA Synthesis, Current Protein & Peptide Science 2010; 11 (6) . https://dx.doi.org/10.2174/138920310791824075
DOI https://dx.doi.org/10.2174/138920310791824075 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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