Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain

Yamashiro, Kyoko; Tsuruoka, Nobuo; Kodama, Shiho; Tsujimoto, Masafumi; Yamamura, Yoshikazu; Tanaka, Takaharu; Nakazato, Hiroshi; Yamaguchi, Naohito

doi:10.1016/s0167-4781(96)00187-x

Cited by 156 publications

(113 citation statements)

References 8 publications

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“…The KLK6 gene (encoding for human kallikrein 6 [hK6]) has been cloned independently by three groups of investigators and was previously given the names zyme (7), protease M (8) and neurosin (9). The gene encodes for a trypsin-like serine protease of 244 amino acids in length, of which sixteen amino acids constitute the signal peptide and five amino acids the activation peptide.…”

Section: Introductionmentioning

confidence: 99%

“…Anisowicz et al have cloned the gene by the method of differential display, based on the significant differences in expression between normal and malignant breast cells and they postulated that this gene is dramatically down-regulated in aggressive forms of breast cancer (8). The same gene was cloned by Yamashiro et al from the human colon adenocarcinoma cell line COLO 201 (9).…”

Section: Introductionmentioning

confidence: 99%

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Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Diamandis¹,

Yousef²,

Soosaipillai³

et al. 2000

Clinical Biochemistry

117

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Diamandis¹,

Yousef²,

Soosaipillai³

et al. 2000

Clinical Biochemistry

117

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“…Previously called zyme (Little et al, 1997), protease M (Anisowicz et al, 1996), and neurosin (Yamashiro et al, 1997), kallikrein 6 is now the accepted name (Diamandis et al, 2000b). hK6 is a trypsin-like serine protease of unknown physiologic function that is secreted as a 223 amino acid protein.…”

mentioning

confidence: 99%

“…Various tissues express the hK6 gene and synthesize the protein (Diamandis et al, 2000c;Yousef et al, 1999). Expression is particularly prominent in the brain (Yamashiro et al, 1997), and this, along with the amyloidogenic potential of hK6 (Little et al, 1997) has raised the possibility of a role for hK6 in amyloid precursor processing and the development of Alzheimer's disease. Recently, Diamandis et al (2000d) have shown that hK6 is elevated in the cerebrospinal fluid and blood of individuals with histologically confirmed Alzheimer's, thereby suggesting hK6 may be of value in the diagnosis of this disorder.…”

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confidence: 99%

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

et al. 2002

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Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg 71 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (435 ng hK6 mg 71 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg 71 total protein) was higher in late stage disease, serous histotype, residual tumour 41 cm and suboptimal debulking (41 cm) (P50.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

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“…hK6 (also known as Zyme/Protease M/Neurosin) was independently cloned by three groups of investigators. Using polymerase chain reaction with degenerative primers for conserved regions in serine protease genes, hK6 was identified from Alzheimer's disease brain and the colon adenocarcinoma cell line colo 201, respectively (Little et al, 1997;Yamashiro et al, 1997). Meanwhile, by differential display, the same gene was cloned from a breast cancer cell line (Anisowicz et al, 1996).…”

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confidence: 99%

Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resistance

et al. 2002

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The human tissue kallikreins are secreted serine proteases, encoded by a group of homologous genes clustered in tandem on chromosome 19q13.3-4. Human kallikrein 6 and human kallikrein 10 are two new members of this family. Recently, we developed highly sensitive and specific immunofluorometric assays for human kallikrein 6 and human kallikrein 10, which allow for their quantification in tissue extracts and biological fluids. Both human kallikrein 6 and human kallikrein 10 are found to be down-regulated in breast cancer cell lines, suggesting that they may be involved in breast cancer pathogenesis and progression. In this study, we investigated the potential value of human kallikrein 6 and human kallikrein 10 as prognostic and predictive factors in breast cancer. We quantified human kallikrein 6 and human kallikrein 10 protein levels in 749 breast tumour cytosolic extracts and correlated this data with various clinicopathological variables and patient outcomes. Human kallikrein 6 and human kallikrein 10 are positively correlated with each other. Higher human kallikrein 6 and human kallikrein 10 protein levels are associated with younger age, pre-menopausal, status and tumours which are negative for oestrogen and progesterone receptors. No correlation was found between human kallikrein 6 and human kallikrein 10 levels and tumour size, grade, and nodal status. Survival analysis showed that neither human kallikrein 6 nor human kallikrein 10 are related to the rate of relapse-free and overall survival. In the analysis with respect to response to tamoxifen therapy, although human kallikrein 6 levels were not associated with tamoxifen responsiveness, higher levels of human kallikrein 10 were significantly associated with a poor response rate. This association remained significant in the multivariate analysis. Furthermore, higher human kallikrein 10 levels were significantly related with a short progression-free and post-relapse overall survival after start of tamoxifen treatment for advanced disease. Taken together, our results suggest that although human kallikrein 6 and human kallikrein 10 are not prognostic markers for breast cancer, human kallikrein 10 is an independent predictive marker for response of tamoxifen therapy.

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Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain

Cited by 156 publications

References 8 publications

Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resistance

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