Prostate specific antigen role and function

Prostate specific antigen (PSA) is considered the most sensitive marker available for monitoring prostate cancer progression and response to therapy. In addition to its value as a tumor marker, PSA may have biologic activities involved in cancer growth. The PSA gene was cloned in the 1980s, and it was recognized that PSA is a serine protease homologous to the kallikreins. The aspartic acid residue in the histidine-aspartic acid-serine triad required for kallikrein-type serine protease specificity has been replaced by serine in PSA, conferring on PSA chymotrypsin-like activity instead of the trypsin-like activity of the kallikreins. The major site of PSA expression is the prostate, where it is secreted by the luminal cells of the epithelium. Most prostate cancers also express PSA. Substrates of PSA in the seminal fluid, where PSA is present at >1 mg/ml and is enzymatically active, include seminogelin and fibronectin. The net effect of PSA activity is to liquefy the seminal fluid after ejaculation, which is presumably of some consequence to fertility. Recently, it was discovered that insulin-like growth factor binding protein-3 (IGFBP3) is cleaved by PSA. The biologic effect of this cleavage is the release of IGF, enhancing its mitogenic capabilities. PSA may also enhance cellular growth by a mechanism independent of proteolytic cleavage of IGFBP3. In summary, the proteolytic activities of PSA have just begun to be investigated, but preliminary findings indicate that PSA has biologic relevance in addition to its value as a clinical marker of prostate cancer. Cancer 1995;75:2021–6.