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Int J Clin Exp Pathol 2(3),267-274;2009

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

Jeremy G. Stone, Raj K. Rolston, Masumi Ueda, Hyoung-gon Lee, Sandy L. Richardson,  Rudy J. Castellani, George Perry, and Mark A. Smith

Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA; Department of Pathology, University of Maryland, Baltimore,
Maryland, USA; College of Sciences, University of Texas at San Antonio, San Antonio, Texas, USA

Received 17 September 2008; Accepted in revision 6 October 2008; Available online 20 October 2008

Abstract: 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 non-prostatic 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. (IJCEP809002).

Key Words: hK3, immunocytochemistry, mRNA, neuron, PCR, prostate specific antigen, protease, protein

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Address all correspondence to: Mark A. Smith, PhD, Department of Pathology, Case Western Reserve University, 2103 Cornell Road,
Cleveland, Ohio 44106 USA, Tel: 216-368-3670, Fax: 216-368-8964, E-mail: