Disease relevance of KLK8

• The KLK8 protein (hK8) is known to be a favorable prognostic marker in ovarian cancer, but the biological basis of this is not understood [1].
• Collectively, these findings show that KLK8 expression confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness [1].
• Patients with higher KLK8 expression in the tumor have lower grade disease, lower residual tumor left after surgery, live longer, and relapse less frequently [2].
• These data were verified by screening the EST databases, where all mRNA clones isolated for these genes, except for one in each, were from normal breast libraries, with no clones detected from breast cancer tissues or cell lines (with the exception of KLK8) [3].
• Our results indicate that elevated TADG-14/KLK8 expression is an early event in endometrial carcinogenesis, and may potentially serve as a useful early biomarker for the detection of endometrial carcinomas in menopausal women [4].

Psychiatry related information on KLK8

• Performance was compared with conditioned blocking (CB) and monoamine metabolic status between healthy controls, patients with obsessive compulsive disorder (OCD) or schizophrenia with (PH) or without (NP) active paranoid hallucinatory symptoms [5].

High impact information on KLK8

• The alpha-defensins (HNP 1-3) were also found to be expressed in several of these cell lines [6].
• After growing these lymphocytes for 5 days in the presence of interleukin (IL)-2, we isolated and characterized several antibacterial peptides/proteins from the supernatant-alpha-defensins (HNP 1-3), LL-37, lysozyme, and a fragment of histone H2B-although other active components were also present [6].
• In addition, we demonstrated that LL-37 has chemotactic activity for polymorphonuclear leukocytes and CD4 T lymphocytes, whereas others have shown chemotactic activity for human alpha-defensins (HNP 1-2) [6].
• These findings suggest that microbicidal peptides are effector molecules of lymphocytes and that antibacterial activity previously shown to be derived from T and NK cells may be partly mediated by the antibacterial peptides LL-37 and HNP 1-3 [6].
• Human defensins (human neutrophil peptides) HNP 1-3 are 29-30 amino acid antibiotic and cytotoxic peptides highly abundant in the cytoplasmic granules of polymorphonuclear leukocytes [7].

Chemical compound and disease context of KLK8

• Tumor-associated differentially expressed gene-14 (TADG-14) is a novel transmembrane serine protease recently reported by our group to be highly overexpressed in ovarian carcinomas [8].

Biological context of KLK8

• In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin [1].
• Genes involved in proteolysis (KLK8) and signal transduction (CRABP2) were found to be downregulated in HPV-positive SCCHN [9].
• The KLK8 gene product, neuropsin, processes extracellular matrix and is important for neuronal plasticity [10].
• In addition, to validate gene expression data at the protein level, TADG-14 expression was evaluated by immunohistochemistry on paraffin-embedded tissue from which all 11 primary tumor cell lines were established [8].
• Influenza A virus released by infected diploid human fibroblasts contains nearly equal amounts of two electrophoretic forms of the viral nucleocapsid protein NP (NP1 and NP2) [11].

Anatomical context of KLK8

• We found that overexpressing the KLK8 gene in highly invasive lung cancer cell lines suppresses their invasiveness [1].
• Kallikrein 8 (KLK8) plays a role in the physiology of the central nervous system [12].
• We demonstrate an 11.5-fold increase in KLK8 mRNA levels in AD hippocampus compared to controls [10].
• TADG-14/KLK8 mRNA expression levels were significantly higher in proliferative compared to secretory phase endometria (p = 0.0143) [4].
• In contrast, none of the normal cervical keratinocyte control cultures (n=4) or flash frozen normal cervical biopsy specimens (n=4) expressed TADG-14 [8].

Associations of KLK8 with chemical compounds

• The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene family, encodes a serine protease [1].
• Thirty to sixty times more pNP than NP was required to obtain equivalent inhibition of Hoechst 33258 binding to DNA [13].
• In HNP, the half-cystine contents of beta 60, alpha 38, alpha 26, and beta 17 were approximately 3, 12, 3, and 4, respectively [14].
• Array analysis showed that exposure of hepatocytes to NP mainly altered genes involved in the estrogenic pathway, including genes for steroid hormone synthesis and metabolism [15].
• Replacement of the introduced alanine residues 40 and 42 by aspartate restored the interaction between VP30 and the NP inclusions pointing to the importance of negative charges at these particular positions [16].

Other interactions of KLK8

• In this study, we examined the level of mRNA expression of the KLK7 and KLK8 genes in 73 intracranial tumors using qualitative RT-PCR [12].
• Experimental evidence has shown that at least two kallikreins, KLK6 and KLK8, have potential functions in the CNS [17].
• KLK8 (neuropsin) is highly expressed in brain tissues and may play a role in brain development, plasticity and response to stress [17].
• In order to address these questions, we studied the expression of glucosylceramides (GlcCer), cathepsin D (CatD), corneodesmosin (Cdsn), kallikrein (KLK)7, and KLK8 in normal human epidermis using confocal laser scanning microscopy and immunoelectron microscopy [18].
• Cloning of tumor-associated differentially expressed gene-14, a novel serine protease overexpressed by ovarian carcinoma [19].

Analytical, diagnostic and therapeutic context of KLK8

• In addition, studies in a mouse model coupled with the detection of circulating tumor cells by quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor growth and invasion in vivo [1].
• In multivariate analysis, higher KLK8 expression was significantly associated with longer disease-free survival [2].
• METHODS: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed [20].
• To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures [20].
• Human kallikrein 8: immunoassay development and identification in tissue extracts and biological fluids [21].

References