PSMA (EP192), RMab

Summary and Explanation

PSMA, prostate specific membrane antigen, is a Type 2 integral membrane glycoprotein found in prostate and a few other tissues. Three functionally-distinct proteins are encoded, including folylpoly-gamma-glutamate carboxypeptidase in the intestine, N-acetylated alpha-linked acidic dipeptidase 1 in the brain and prostate specific membrane antigen in the prostate. A mutation in the intestinal form may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. The form expressed in the brain may be involved in a number of pathological conditions associated with glutamate cytotoxicity. The prostate form is up-regulated in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants.

Although PSMA antibody expression is highest in the prostate, detectable levels of protein are also found in the small intestine and the brain. PSMA is expressed in prostate cancer cells as a noncovalently associated homodimer. Using a secreted form of the protein, it has been demonstrated that the extracellular domain is sufficient for dimerization and that dimerization is required for enzymatic activity. When used as an immunogen, dimeric (but not monomeric) PSMA is capable of efficiently eliciting antibodies that recognize PSMA-expressing tumor cells. It is a possible therapeutic target for prostate cancer and it is being used (with radioactive antibodies) to image prostate tissue.