Expression of a kallikrein-like protein in prostatic intraepithelial neoplasia in ventral prostate of the noble rat

BACKGROUND. In an effort to identify biomarker(s) for prostatic cancer (PCa ), we analyzed the changes of secretory proteins in the ventral prostate (V P) of Noble rats at early stages of carcinogenesis. METHODS. Ventral prostates were removed from both control (n = 36) and expe rimental (n = 88) rats implanted with a known ratio of testosterone (T) and 17 beta-estradiol (E-2). Tissue sections were stained by hematoxylin and e osin (H&E) for pathological screening, and secretions were collected for SD S-PAGE analysis followed by N-terminal microsequencing, antiserum productio n, Western blot, and immunohistochemical study. RESULTS. Pathologically, low-grade prostatic intraepithelial neoplasia (LGP IN) and high-grade PIN (HGPIN) were observed in ducts or alveoli after 3 an d 5 months of T + E-2 treatment, respectively. The results of SDS-PAGE show ed an elevated expression of 18-kDa protein (p18) in secretions of VP with HGPIN or cancerous lesions. Analysis of p18 by N-terminal sequencing showed a high score of homology to rat glandular kallikrein. To characterize the expression pattern of the protein in tissue samples, an antiserum was raise d against the N-terminus of the p18. The monospecificity of the antiserum a gainst p18 was confirmed by Western blot analysis. Immunohistochemical stud y showed that in ducts or alveoli of normal and LGPIN samples, a mild posit ive staining for p18 was observed in secretions. However, the reactivity wa s intense not only in luminal secretions but also in some luminal secretory cells in HGPIN and cancer cells as well. CONCLUSIONS. The high expression of p18 in connection with neoplastic trans formation of cells strongly suggests that the potential application of this protein as a marker for early detection of PCa should be further investiga ted. Prostate 42:8-17, 2000. (C) 2000 Wiley-Liss, Inc.