Disease relevance of KLK11

• Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines [1].
• Human kallikrein gene 11 (KLK11) mRNA overexpression is associated with poor prognosis in patients with epithelial ovarian cancer [2].
• The mean value of relative KLK11 expression ratio was significantly higher in ovarian tumor samples than in normal ovary samples (compared with normal samples: adenoma, P = 0.0006; low malignant potential tumor, P = 0.0049; and carcinoma, P < 0.0001) [2].
• EXPERIMENTAL DESIGN: KLK11 mRNA expression was examined by semiquantitative PCR in 64 epithelial ovarian tumors (7 adenomas, 6 low malignant potential tumors, and 51 adenocarcinomas) and in 10 normal ovaries [2].
• Quantitative analysis of KLK10 and KLK11 expression levels was assessed by real-time PCR, in a cohort of 47 patients with non-small-cell lung cancer (NSCLC) [3].

High impact information on KLK11

• Ultrastructural demonstration of trypsin-like protease in acrosomes of sea urchin sperm [4].
• Tosyl-lysyl chloromethyl ketone inhibited the trypsin-like protease activity and diminished CPT-induced apoptosis [5].
• The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond [6].
• Thus, resting human lymphocytes contain a trypsin-like protease that is stimulated by nucleotides or pyrophosphate to selectively degrade histone H1 [7].
• Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry [8].

Chemical compound and disease context of KLK11

• A trypsin-like protease in Pronase, clostripain as a contaminant in a commercial preparation of Clostridium histolyticum collagenase, and cysteine proteases in Porphyromonas gingivalis could be detected [9].
• Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells to the bronchial epithelium of rat, proteolytically activates the infectivity of influenza A virus [H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma (1992) J. Biol. Chem. 267, 13573-13579] [10].
• Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein [11].

Biological context of KLK11

• CONCLUSIONS: We conclude that down-regulation of the KLK11 gene in advanced and more aggressive tumors may open the possibility of being used as a future biological marker distinguishing the tumor aggressiveness as well as a useful prognostic biomarker for prostate cancer [12].
• Significant sequence homologies were found between TLSP and other human kallikreins [13].
• There was an increased intensity of KLK11 gene expression in the stratum compactum on day 10 of the estrous cycle and early pregnancy [14].
• Homology search using the amino acid sequence revealed that prostate-type hippostasin was identical to TLSP (PRSS20), which is expressed in human primary keratinocytes (1) [15].
• The difference of 5' nucleotide sequence resulted in the variation in the amino terminal ends of the two, brain and prostate, types of human hippostasin [15].

Anatomical context of KLK11

• TLSP is expressed in many tissues including cerebellum, prostate, salivary glands, stomach, lung, thymus, small intestine, spleen, liver, and uterus [13].
• RESULTS: KLK11 mRNA expression was detected in various human cancer tissues including breast, lung, colon, prostate, pancreas, and ovarian carcinoma [2].
• Hippostasin protein was localized in the prostate secretory epithelium, and western blotting showed that hippostasin was present in semen [1].
• RESULTS: Hippostasin mRNA is expressed preferentially in the normal prostate and weakly in the testis [1].
• These results indicated that TLSP/hippostasin is involved in the functions of the human central nervous system and prostate and that it is a multifunctional protease present in various organs [15].

Associations of KLK11 with chemical compounds

• Genomic organization, mapping, tissue expression, and hormonal regulation of trypsin-like serine protease (TLSP PRSS20), a new member of the human kallikrein gene family [13].
• TLSP expression appears to be regulated by steroid hormones in the breast carcinoma cell line BT-474 [13].
• 8. Functional characterization of beta-HMT suggests that it is not a trypsin-like protease, since neither alpha,N-tosyl-L-lysylchloromethylketone nor alpha,N-tosyl-L-arginyl methyl ester are capable of causing significant inhibition of the cell-lytic activity of the molecule [16].
• When baby hamster kidney (BHK) cells were grown in medium containing leupeptin, a potent serine-cysteine protease inhibitor, the trypsin-like protease activity (PABI) in the cells increased its level more than 100-fold over the control [17].
• Extraction of the adenylate cyclase-activating factor of bovine sperm and its identification as a trypsin-like protease [18].

Physical interactions of KLK11

• Some biologic effects of this activator appear to be due to a trypsin-like protease attached to alpha 2M [19].

Enzymatic interactions of KLK11

• This protease significantly hydrolyzed the fluorogenic synthetic substrates for trypsin-like protease but little hydrolyzed those for chymotrypsin-like protease [20].

Regulatory relationships of KLK11

• Furthermore, we demonstrate that KLK12 is able to activate KLK11 zymogen in vitro [21].
• Hence, it seems that a specific membrane-associated trypsin-like protease activity induced by IFN-gamma may play a role in the action of the cytokine on thymidine incorporation in WISH cells [22].
• Histatin 5 strongly inhibited a trypsin-like protease produced by Bacteroides gingivalis with an IC50 value of 55 nM [23].

Other interactions of KLK11

• Several other kallikreins, including kallikreins 2 (KLK2) and 11 (KLK11) are emerging as complementary prostate cancer biomarkers [24].
• Serum total PSA concentration was found to be lower in patients with overexpression of KLK11 (p = 0.044) [12].
• PURPOSE: The purpose of this study was to examine expression levels of the human tissue kallikrein 11 gene (KLK11) in epithelial ovarian tumors and to identify the relationship between KLK11 expression and patient survival [2].
• The enzyme activity was similar to that of brain-type hippostasin, which has kallikrein-like activity [25].
• Two types of KLK11 isoforms, isoform 1 and isoform 2, have been predicted from cDNA sequences [26].

Analytical, diagnostic and therapeutic context of KLK11

• METHODS: In the present study, the expression of prostate type variant of KLK11 gene was analyzed by RT-PCR in 66 prostate cancer tissues [12].
• KLK11 was amplified by PCR using gene specific primers and its identity was verified by sequencing [12].
• Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate [25].
• We analyzed the expression of the prostate-type variant of the KLK11 gene in 64 CaP and BPH tissues obtained by transrectal ultrasound-guided needle biopsy [27].
• A trypsin-like protease was purified from spent culture medium of oral pathogen Porphyromonas gingivalis by chromatography on columns of DEAE-Sepharose, gel filtration on Sephadex G-100, and chromatofocusing on PBE-94 [28].

References