A novel serine protease highly expressed in the pancreas is expressed in various kinds of cancer cells

Abstract

We have isolated a cDNA that encodes a novel serine protease, prosemin, from human brain. The cDNA of human prosemin is 1306 bp, encoding 317 amino acids. It showed significant homology with the sequence of a chromosome 16 cosmid clone (accession no. ). The prosemin gene contains six exons and five introns. The amino acid sequence of prosemin shows significant homology to prostasin, γ‐tryptase, and testisin (43%, 41%, and 38% identity, respectively), the genes of which are also located on chromosome 16. Northern hybridization showed that prosemin is expressed predominantly in the pancreas and weakly in the prostate and cerebellum. However, western blot and RT‐PCR analyses showed that prosemin is expressed and secreted from various kinds of cancer cells, such as glioma, pancreas, prostate, and ovarian cell lines. Prosemin is secreted in the cystic fluid of clinical ovarian cancers. Furthermore, immunohistochemistry showed prosemin protein localized in the apical parts of ovarian carcinomas. Recombinant prosemin was expressed in COS cells and was purified by immunoaffinity chromatography. Recombinant prosemin preferentially cleaved benzyloxycarbonyl (Z)‐His‐Glu‐Lys‐methylcoumaryl amidide (MCA) and t‐butyloxycarbonyl (Boc)‐Gln‐Ala‐Arg‐MCA. Our results suggest that prosemin is a novel serine protease of the chromosome 16 cluster that is highly expressed in the pancreas. The usefulness of this serine protease as a candidate tumor marker should be further examined.

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

“…Whereas KLK11 gene expression is regulated in a tissue‐specific manner, recent reports suggest that tumorigenesis disturbs the regulation of the gene's expression [1–4,24]. Together with our previous report that prostate cancer cells express only isoform 1, but not isoform 2 [14], promoter 2 is possibly inactivated in cancer cells.…”

C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer

“…NM_002774; ref. 8). Several novel genes were also identified, including C35, which were overexpressed at levels > 10-fold in the breast tumors.…”

Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling

“…To determine the specific functions of BSSP4, control cell lines (Figure  2A, Huh7-control #1 and #2) and those overexpressing BSSP4 (Figure  2A, Huh7-BSSP4 #1 and #2) were established. BSSP4 has been detected in several cancer types [9]. The protein was originally identified as a member of the human serine protease family, also designated tryptase ϵ [7].…”

“…The uPA system, a serine protease family comprising tissue-type plasminogen activator (tPA), uPA, uPA receptor (uPAR) and plasminogen activator inhibitors (PAIs), is universally found in almost all cancer types [8]. While BSSP4 has been shown to play a role in different cancers [9], few studies to date have focused on its specific functions in cancer biology.…”