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• W3049272837 abstract "3940 Prostate specific membrane antigen (PSMA) is of intense interest as a prostate cancer marker and for its potential as a diagnostic and therapeutic target in humans. This protein is a type II transmembrane glycoprotein that is predominantly expressed in prostate cancers, whereas normal and benign prostate tissues mainly express a shorter alternatively spliced variant, designated PSM’. Mice that express human PSMA in their prostates have been shown to develop precancerous lesions whereas mice that express human PSM’ do not develop such lesions. PSMA has a unique folate hydrolase activity whereas PSM’ exists in the cell cytoplasm and has no enzymatic activity. These findings suggest that PSMA plays a role in prostate carcinogenesis and that the enzymatic activity and/or the extracellular location of PSMA are important. A mechanism by which PSMA might be involved in prostate carcinogenesis is via its folate hydrolase activity. It is thought that this membrane folate hydrolase could give prostate cancer cells expressing PSMA a growth advantage in a low folate tumor microenvironment by allowing these cells to capture extracellular folates and deglutamate poly-γ-glutamated folates released by surrounding dead and dying cells. Folate taken up by these cells is an essential nutrient for growth and replication. Other researchers who have investigated if PSMA confers a growth advantage have found no such effect. However, their studies were flawed as they were carried out in standard tissue culture media which contain folate at a concentration 100 times greater than the folate concentration in human sera. The purpose of this study was firstly to examine whether PSMA gives a human prostate cancer cell line expressing PSMA a growth advantage in physiologically relevant folate level in the presence of poly-γ-glutamated folates. Secondly, by using a folate hydrolase inhibitor we examined if the folate hydrolase activity of PSMA is the mechanism by which it give cells a growth advantage. The proliferation rates of LNCaP and DU-145 cells were assessed when grown in RPMI 1640 media containing either low ( in vitro , PSMA expression confers a growth advantage in physiological folate level in the presence of penta-γ-glutamated folate via the folate hydrolase activity of PSMA. This study will provide a better understanding of the molecular events that underlie prostate carcinogenesis which may be useful in designing therapies that target PSMA." @default.
• W3049272837 created "2020-08-21" @default.
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• W3049272837 date "2005-05-01" @default.
• W3049272837 modified "2023-09-26" @default.
• W3049272837 title "The mechanism by which prostate specific membrane antigen (PSMA) may induce prostate carcinogenesis and growth" @default.
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