Role of PSMA in Aberrant Cell Cycle Progression in Prostate Cancer

PSMA, a transmembrane glycoprotein of approximately 100kD, is expressed in prostate epithelial cells (Horoszewicz et al., 1987; Israeli et al., 1993). In addition to being expressed in non-neoplastic prostate epithelium, PSMA is expressed by a very high proportion of prostate cancers. Expression is further increased in higher-grade cancers and metastatic disease, and in hormone-refractory prostate cancers (Wright et al., 1995). PSMA is a type II membrane protein with a short N-terminal cytoplasmic tail and a large C-terminal extracellular domain (Israeli et al., 1993). The extracellular domain of PSMA has several potential N-glycosylation sites and shows homology (54% at nucleic acid level) to the transferrin receptor. PSMA is homologous to glutamate carboxypeptidase II (85% at nucleic acid level) and has been suggested to have folate hydrolase activity and N-acetylated alpha-linked acidic dipeptidase (NAALADase) activity (Pinto et al. 1996; Luthi-Carter et al., 1998). Abundance of PSMA expression in prostate cancer cells suggests that PSMA expression might be associated with events involved in prostate cancer progression (Rajasekaran et al.,2005).
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