Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate.

Hippostasin is a kallikrein-like serine protease, which has two alternatively spliced isoforms, brain-type and prostate-type. We previously reported alternative expression of hippostasin in prostate cancer cell lines. We studied the expression of a variant-form hippostasin (isoform 3) mRNA by RT-PCR. Localization of the isoform 3 protein was examined by immunohistochemistry. The enzymatic activity of the recombinant protein was measured with synthetic substrates. A novel isoform of hippostasin contains 25 additional amino acids in the catalytic triad of brain-type hippostasin. Its mRNA was expressed in normal prostate tissue, BPH, and prostate cancer cell lines. The protein was localized in the prostate secretory epithelium. The enzyme activity was similar to that of brain-type hippostasin, which has kallikrein-like activity. In this study, we have identified a third isoform of hippostasin, which was designated variant-form (isoform 3). Hippostasin isoform 3 may play a role in the prostate, including reproductive and/or tumorigenic functions.

Nakamura T ，Mitsui S ，Okui A ，Miki T ，Yamaguchi N ... -  《PROSTATE》

A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate.

Mitsui S ，Yamada T ，Okui A ，Kominami K ，Uemura H ，Yamaguchi N ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

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

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. 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. 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 Our results suggest the possibility that hippostasin may be a useful marker by which prostate cancer and BPH can be distinguished.

Nakamura T ，Mitsui S ，Okui A ，Kominami K ，Nomoto T ，Ukimura O ，Kawauchi A ，Miki T ，Yamaguchi N ... -  《PROSTATE》

Multiple promoters regulate tissue-specific alternative splicing of the human kallikrein gene, KLK11/hippostasin.

Mitsui S ，Nakamura T ，Okui A ，Kominami K ，Uemura H ，Yamaguchi N ... -  《FEBS Journal》

Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues.

Nakamura T ，Stephan C ，Scorilas A ，Yousef GM ，Jung K ，Diamandis EP ... -  《-》