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Stabilizing Androgen Receptor in Mitosis Inhibits Prostate Cancer Proliferation
Donald J. Vander Griend, Ivan V. Litvinov and John T. Isaacs
volume 6 | issue 6
15 March 2007Pages: 647 - 651
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The Androgen Receptor (AR) is a steroid transcription factor, the activity of which is the primary focus of androgen ablation therapies for advanced prostate cancer. In prostate cancers, the AR acquires gain-of-function changes allowing it to drive prostate cancer cell survival and proliferation in a cell-autonomous manner. As part of this malignancy-associated gain-of-function, AR acquires a role in licensing for DNA replication in prostate cancer cells. In its role as a licensing factor, AR must be degraded during mitosis in order to allow re-licensing in the subsequent cell cycle. This conclusion is supported by the demonstration that acute enhanced expression of AR in prostate cancer cells results in its incomplete degradation in mitosis. This lack of mitotic AR degradation inhibits subsequent cell proliferation due to the inability to re-license all origins of replication needed for the next round of cell division. These data provide a unifying paradigm to clarify a number of unresolved observations in prostate cancer research. In addition, they provide a rationale for a new therapeutic approach for prostate cancer based upon stabilization of AR.
Authors
Donald J. Vander Griend
The Johns Hopkins University School of Medicine; Baltimore, MD USA
Ivan V. Litvinov
The Johns Hopkins University School of Medicine; Baltimore, MD USA
John T. Isaacs
The Johns Hopkins University School of Medicine; Baltimore, MD USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.