Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines

Background. Hippostasin is a kallikrein-like protease (PRSS20/KLK11), which is expressed preferentially in the hippocampus and prostate. We have reported that alternative splicing variants of human hippostasin are regulated in a tissue-specific manner. Brain-type hippostasin consists of 250 amino acids including a typical signal sequence, and is expressed in the brain and prostate. The prostate-type hippostasin, which has 32 extra amino acids at the N-terminal end, is expressed only in the prostate. Methods. We analyzed the expression and localization of hippostasin in normal prostate tissue, BPH tissue, and prostate cancer cell lines. We performed northern blotting, in situ hybridization, immunohistochemistry, and RT-PCR. Results. Hippostasin mRNA is expressed preferentially in the normal prostate and weakly in the testis. It was detected in prostate secretory epithelium. Hippostasin protein was localized in the prostate secretory epithelium, and western blotting showed that hippostasin was present in semen. All tested prostate cancer cell lines, including PSA-negative cell lines, expressed hippostasin. Interestingly, all the prostate cancer cell lines expressed only brain-type but not prostate-type hippostasin, while normal prostate and BPH expressed both types of hippostasin. Conclusions. Our results suggest the possibility that hippostasin may be a useful marker by which prostate cancer and BPH can be distinguished Prostate 49: 72-78, 2001. (C) 2001 Wiley-Liss, Inc.