PROSTATE-SPECIFIC ANTIGEN ROLE AND FUNCTION

Prostate specific antigen (PSA) is considered the most sensitive marke r available for monitoring prostate cancer progression and response to therapy. In addition to its value as a tumor marker, PSA may have bio logic activities involved in cancer growth. The PSA gene was cloned in the 1980s, and it was recognized that PSA is a serine protease homolo gous to the kallikreins. The aspartic acid residue in the histidine-as partic acid-serine triad required for kallikrein-type serine protease specificity has been replaced by serine in PSA, conferring on PSA chym otrypsin-like activity instead of the trypsin-like activity of the kal likreins. The major site of PSA expression is the prostate, where it i s secreted by the luminal cells of the epithelium. Most prostate cance rs also express PSA. Substrates of PSA in the seminal fluid, where PSA is present at >1 mg/ml and is enzymatically active, include seminogel in and fibronectin. The net effect of PSA activity is to liquefy the s eminal fluid after ejaculation, which is presumably of some consequenc e to fertility. Recently, it was discovered that insulin-like growth f actor binding protein-3 (IGFBP3) is cleaved by PSA. The biologic effec t of this cleavage is the release of IGF, enhancing its mitogenic capa bilities, PSA may also enhance cellular growth by a mechanism independ ent of proteolytic cleavage of IGFBP3. In summary, the proteolytic act ivities of PSA have just begun to be investigated, but preliminary fin dings indicate that PSA has biologic relevance in addition to its valu e as a clinical marker of prostate cancer.