Evidence for the novel expression of human kallikrein-related peptidase 3, prostate-specific antigen, in the brain.

Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. With chymotrypsin-like enzymatic activity, hK3 is directly and indirectly involved in a number of diverse biological functions including male fertility, the regulation of cell proliferation, and the inhibition of angiogenesis. The gene encoding hK3, hKLK3, is located on chromosome 19 and its expression has been shown to be regulated by steroid hormones through androgen receptor-mediated transcription. hK3 was once thought to be exclusively expressed and secreted by prostatic epithelial cells, hence the initial name of prostate-specific antigen, but has since been isolated in several nonprostatic tissues and ongoing characterization of alternative splicing variants has found at least 13 distinct mRNA transcripts. The detection of hK3 in cerebrospinal fluid prompted the hypothesis that hK3 may be produced in the brain. To test this notion, in this study we used RT-PCR amplification of brain tissue total RNA and examined hK3 protein by immunohistochemical, and immunoblot analysis. RT-PCR revealed several hK3 mRNA transcripts in the brain. Confirming these findings, both immunohistochemical staining and western immunoblotting showed evidence for hK3 protein in neuronal cells. Taken together, our findings support the expression of hK3 in neuronal cells reinforcing the concept of hK3 as a ubiquitous protein with more multifarious biological activity than previously believed. Ongoing research seeks to elucidate the functional significance of hK3 in brain cells.