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

Nakamura, Toshio; Mitsui, Shinichi; Okui, Akira; Kominami, Katsuya; Nomoto, Takuya; Ukimura, Osamu; Kawauchi, Akihiro; Miki, Tsuneharu; Yamaguchi, Naohito

doi:10.1002/pros.1119

Cited by 35 publications

(20 citation statements)

References 16 publications

(21 reference statements)

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“…Isoform 1 is preferentially expressed in the central nervous system, whereas isoform 2 is expresseed in both types. Interestingly, most of prostate cancer cell lines express only isoform 1 [8].…”

Section: Introductionmentioning

confidence: 99%

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

Nakamura¹,

Mitsui²,

Okui³

et al. 2003

The Prostate

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Section: Introductionmentioning

confidence: 99%

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

Nakamura¹,

Mitsui²,

Okui³

et al. 2003

The Prostate

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“…The prosemin gene contains six exons and five introns. The amino acid sequence of prosemin shows significant homology to prostasin, c-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.…”

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confidence: 99%

“…Serum neurosin levels are elevated specifically in patients with ovarian cancer [15]. Furthermore, we have previously reported that the alternative splicing of hippostasin is regulated in a cancer‐specific manner [16]. In addition, serum levels of hippostasin are increased in patients with ovarian and prostate cancers [17].…”

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confidence: 99%

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

Mitsui¹,

Okui²,

Kominami³

et al. 2005

The FEBS Journal

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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.

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“…Slawin et al [18] reported the prognostic significance of a splice-variant-specific RT-PCR for KLK2, in detecting prostate cancer metastasis. Nakamura et al [19] reported differential expression of the brain and prostate types of KLK11 between benign, hyperplastic and malignant prostate cancer cell lines. A novel, ovarian cancer-specific variant of KLK5 has been recently reported [13].…”

Section: Discussionmentioning

confidence: 99%

The Kallikrein Gene 5 Splice Variant 2 Is a New Biomarker for Breast and Ovarian Cancer

Yousef¹,

White²,

Kurlender³

et al. 2004

Tumor Biol

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The presence of more than one mRNA form for the same gene is common among kallikreins, and many of the kallikrein splice variants may hold significant clinical value. The human kallikrein gene 5 (KLK5) is a member of the human kallikrein gene family of serine proteases on chromosome 19q13.4. KLK5 has been shown to be differentially expressed in a variety of endocrine tumors including ovarian, breast and prostate cancer. Utilizing Expressed Sequence Tag database analysis and reverse transcriptase polymerase chain reaction, we identified a new alternatively spliced form of KLK5(KLK5-splice variant 2, KLK5-SV2). This variant mRNA is 1,438 bp in length; formed of 195 bp of 5′ untranslated region, 882 bp of protein coding sequence and a 3′ untranslated region of 326 nucleotides. KLK5-SV2 has 7 exons, the first 2 of which are untranslated, and 6 intervening introns. KLK5-SV2 is different from the classic form of the KLK5 mRNA in its 5′ untranslated region, where the first 5′ untranslated exon of the classic form is split into 2 exons with an intervening intron of 135 nucleotides. KLK5-SV2 is expressed in a variety of tissues, with higher expression levels in the mammary gland, cervix, salivary gland and trachea. The steroid hormone receptor-positive breast cancer cell line BT-474 was used to examine the effect of different steroids on the expression levels of KLK5-SV2. Expression levels were significantly higher after stimulation with androgens, but not estrogens, progestins, aldosterone or corticosteroids. While relatively high levels of expression were found in all 10 normal breast tissues examined, no expression was detected in 16 breast cancer tissues, and expression was significantly lower than normal in the remaining 4 cancers. Expression levels comparable to normal were found in only 1 breast cancer cell line. Weak to no expression was detected in 3 other breast cancer cell lines. KLK5-SV2 was not detectable in any of the 10 normal ovarian tissues examined. It was, however, expressed at relatively high levels in 10 out of 20 ovarian cancer tissues, and lower levels were found in 4 other cancers. No expression was detected in the remaining 6 cancers. High expression levels were also detected in the CAOV-3 ovarian cancer cell line. KLK5-SV2 is a potential biomarker for breast and ovarian cancers.

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

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

Cited by 35 publications

References 16 publications

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

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

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

The Kallikrein Gene 5 Splice Variant 2 Is a New Biomarker for Breast and Ovarian Cancer

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