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Dose of PTEN protein found to determine progression of prostate cancer

NEW YORK, NY October 27 - In patients with prostate cancer, one change that can be seen at the molecular level is the loss of the PTEN tumor suppressor gene, a gene responsible for restricting cell proliferation. One or both copies of the PTEN gene are found to have been lost in 70 percent of prostate cancer patients at the time of diagnosis. It has generally been believed that one remaining copy would still protect against tumor progression to advanced metastatic cancer.

But now, for the first time, scientists at Memorial Sloan-Kettering Cancer Center have established mouse models for prostate cancer that have varying "doses" or amounts of Pten protein produced from the remaining gene. Their results show that the activity of the single Pten gene does not necessarily protect against prostate cancer. Instead, the dose determines whether the tumor will become either an aggressive cancer or take a slow path towards microscopic features of growth, but remain benign. This new understanding of the natural history of the disease could allow researchers to develop novel clinical strategies to diagnose, treat, and possibly prevent prostate cancer. This article will appear both as HTML and in print in the December 23, 2003 issue of the new, open access journal published by the Public Library of Science. It appears in PDF form online as a pre-issue publication on October 27, 2003 at www.plosbiology.org.

"We have shown that prostate cancer development is not just affected by mutation and loss of the PTEN gene but that its progression is dose-dependent on the PTEN protein, which we have measured for the first time," said Pier Paolo Pandolfi, M.D., Ph.D., Head of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering and the study's senior author. "Two men, each with one PTEN gene left, could have totally different disease outcomes depending on the actual dose of PTEN protein coming from that ge
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Contact: Joanne Nicholas
mediastaff@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
27-Oct-2003


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