Evolutionary History of Tissue Kallikreins

Pavlopoulou, Athanasia; Pampalakis, Georgios; Michalopoulos, Ioannis; Sotiropoulou, Georgia

doi:10.1371/journal.pone.0013781

Cited by 57 publications

(105 citation statements)

References 106 publications

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“…The human kallikrein 1 (KLK1) protein sequence was used as a query to search the genome of Xenopus tropicalis (frog) in the ENSEMBL database. The hit with the highest score was the sequence ENSXETP00000006440 which, in a previous study (24), was shown to be a bona fide KLK1.…”

Section: Phylogenetic Analysismentioning

confidence: 94%

State-of-the-art bioinformatics protein structure prediction tools (Review)

Michalopoulos

2011

Int J Mol Med

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Abstract. Knowledge of the native structure of a protein could provide an understanding of the molecular basis of its function. However, in the postgenomics era, there is a growing gap between proteins with experimentally determined structures and proteins without known structures. To deal with the overwhelming data, a collection of automated methods as bioinformatics tools which determine the structure of a protein from its amino acid sequence have emerged. The aim of this paper is to provide the experimental biologists with a set of cutting-edge, carefully evaluated, user-friendly computational tools for protein structure prediction that would be helpful for the interpretation of their results and the rational design of new experiments.

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Section: Phylogenetic Analysismentioning

confidence: 94%

State-of-the-art bioinformatics protein structure prediction tools (Review)

Michalopoulos

2011

Int J Mol Med

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“…[50,53,57,58]. Furthermore, KLKs are encoded by the largest contiguous cluster of proteaseencoding genes in the human genome, and uniquely, they are not interrupted by any other non-KLK genes [49,50,57,59,60].…”

Section: General Overviewmentioning

confidence: 99%

“…KLK gene transcripts code for a single chain serine protease pre-proenzyme of a fixed length, between 248 and 293 amino acids [50,57].…”

Section: General Overviewmentioning

confidence: 99%

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Expression of Human Tissue Kallikreins (KLKs) in Polymorphous Low Grade Adenocarcinoma (PLGA)

Cox

2014

Journal of Oral and Maxillofacial Surgery

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Polymorphous low grade adenocarcinoma (PLGA) is the second most common malignant salivary gland tumour of the minor salivary glands. Human tissue kallikreins (KLKs) are a family of highly conserved serine proteases expressed by various tissues throughout the body. KLKs have become powerful tumour markers for the diagnosis of the cancer patient (e.g. PSA (KLK3)). The literature demonstrates a link between KLKs and salivary gland neoplasms. The purpose of this study is to determine levels of KLK mRNA in tissue samples of formalin fixed paraffin embedded polymorphous low grade adenocarcinoma (PLGA). Secondly, we wish to determine if KLK expression is limited to tumour cells alone.Nineteen cases of PLGA were reviewed . A diagnosis of PLGA was confirmed, demographic data was collected, and formalin fixed paraffin-embedded PLGA and normal salivary gland tissue samples were obtained. RNA isolation was achieved, followed by conversion to complementary DNA via reverse transcription. Synthesized DNA primers were added to target kallikrein DNA and through PCR, the quantitative level of expression of KLKs 1-15 was recorded. Samples exhibiting high and low KLK expression were selected for immunohistochemistry staining, using a standard protocol.Results from PCR data reveals statistically significant increase in the mean KLK mRNA expression for KLK1, KLK4, KLK10, KLK12 and KLK15 in PLGA tissue samples, as compared with normal salivary gland tissue (Mann Whitney U test, p<0.05).Immunohistochemistry results demonstrate tumour specific staining. Notably, all samples demonstrating relatively higher KLK mRNA expression showed equivalent or increased staining grade scores relative to the low KLK mRNA expression samples, with respect to a specific KLK.In tissue samples of polymorphous low grade adenocarcinoma there is an increase of KLK1, KLK4, KLK10, KLK12 and KLK15 mRNA relative to normal salivary gland tissue. Furthermore, the tumour cells stain positively and specifically for kallikreins.

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“…The KLK locus, which features among the seven highly-ranked susceptibility loci in a multi-stage prostate cancer GWAS , is clustered in a tan dem array of approximately 300 kilobases (kb) on chromosome 19q13.4, and contains the largest cluster of 15 homologous protease genes (Lawrence et al , 2010 ) said to have evolutionarily emerged 330 million years ago (Clements , 2008 ;Pavlopoulou et al , 2010 ). With the recent imperative given to research on the KLK gene locus, many significant gene -disease associations have been established and previously unknown roles of KLK proteins elaborated.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

Batra

O’Mara²,

Patnala

et al. 2012

Biological Chemistry

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Abstract:The Kallikrein ( KLK ) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

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Evolutionary History of Tissue Kallikreins

Cited by 57 publications

References 106 publications

State-of-the-art bioinformatics protein structure prediction tools (Review)

State-of-the-art bioinformatics protein structure prediction tools (Review)

Expression of Human Tissue Kallikreins (KLKs) in Polymorphous Low Grade Adenocarcinoma (PLGA)

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

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