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Review ArticleReview

The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents

Shannon C. Dixon, Kevin B. Knopf and William D. Figg
Pharmacological Reviews March 2001, 53 (1) 73-92;
Shannon C. Dixon
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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Kevin B. Knopf
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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William D. Figg
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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Abstract

Prostate-specific antigen is a serine protease that is a member of the kallikrein family. It is widely used as an indicator of tumor burden and as a surrogate marker for disease progression in men with androgen-independent prostate cancer. It has been shown that the expression and/or secretion of this glycoprotein can be regulated by pharmacological agents. The effects of these agents on PSA may be independent of their effects on cell growth. For example, a pharmacological agent may down-regulate PSA expression/secretion but have no effect on tumor cell growth. In this case, a patient receiving this therapeutic agent might be falsely considered as having a clinical response. Alternatively, an agent might up-regulate PSA expression/secretion and have an inhibitory effect on cell growth. A patient receiving this therapeutic agent might be diagnosed with progressive disease unless an alternative method for assessing tumor burden is used. Thus, when an agent is to be evaluated in a clinical trial utilizing PSA as a marker for disease progression, it is important to prospectively test whether the agent has an effect on PSA expression and/or secretion. In addition, it is equally important to understand how these regulatory effects relate to cell growth. The purpose of this review is to describe several agents that have been tested for their regulatory effects on PSA and to discuss potential mechanisms of by which this regulation may occur. The implications of these findings in the evaluation of new agents in androgen-independent prostate cancer will be considered.

Footnotes

  • ↵1 Address for correspondence: Dr. William D. Figg, Medicine Branch, DCS, NCI, National Institutes of Health, 10 Center Drive, Building 10, Room 5A01, Bethesda, MD 20892. E-mail:wdfigg{at}helix.nih.gov

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Pharmacological Reviews: 53 (1)
Pharmacological Reviews
Vol. 53, Issue 1
1 Mar 2001
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Review ArticleReview

The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents

Shannon C. Dixon, Kevin B. Knopf and William D. Figg
Pharmacological Reviews March 1, 2001, 53 (1) 73-92;

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Review ArticleReview

The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents

Shannon C. Dixon, Kevin B. Knopf and William D. Figg
Pharmacological Reviews March 1, 2001, 53 (1) 73-92;
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  • Article
    • Abstract
    • I. Introduction
    • II. Model Systems for Studying Prostate-Specific Antigen Regulation
    • III. Overview of Prostate-Specific Antigen Gene Regulation by the Androgen Receptor
    • IV. Agents That Up-Regulate Prostate-Specific Antigen
    • V. Agents That Down-Regulate Prostate-Specific Antigen
    • VI. Agents That Have a Dual Effect On Prostate-Specific Antigen
    • VII. Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
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