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Protein that suppresses androgen receptors could improve prostate cancer diagnosis, treatment
Date:5/20/2009

aka, a Georgia Cancer Coalition Distinguished Cancer Scholar.

Their studies in human tissue both in culture and transplanted into mice show this appears the case for βarrestin2. First the team identified βarrestin2 as cofactor for androgen receptors. Next they found a reciprocal relationship: androgen receptor expression is low when βarrestin2 expression increases. That's the scenario in healthy prostate cells while the exact opposite is true in some prostate cancer. When they forced increased expression of βarrestin2, androgen receptor expression and activity went down.

βarrestin2 locks up an androgen receptor by binding to it, then the pair bind to yet another protein, ubiquitin ligase, which tags the receptor as waste and the trio make their way to the cell's garbage dump. "The neat thing about it is βarrestin2 inhibits or blunts the androgen receptor by promoting its degradation. So it disappears," Dr. Daaka says.

His future studies include determining what happens when βarrestin2 expression is further decreased in the face of prostate cancer. These studies will also help determine how big a player βarrestin2 is in prostate cancer progression, says Dr. Daaka, noting that numerous other corepressors and activators of androgen receptors are known.

Since all the happenings occur inside prostate cells, the findings don't point toward a new blood or urine test for prostate cancer but could lead to new ways to stage prostate cancer from the first biopsy. In fact, Dr. Daaka and his team already are collecting samples from patients whose cancer has been staged to see if specific levels of βarrestin2 expression correlate with different stages of disease.

Another goal is to develop a small molecule that can get inside a patient's cell and mimic βarrestin2's ability to suppress androgen receptor expression and so restore healthy levels found in prostate cells.

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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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