981 research outputs found
Kallikrein Gene Expression in the Gonadotrophin-stimulated Rat Ovary
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The kallikreins (KLKs) are a highly conserved multi-gene family of serine proteases that are expressed in a wide variety of tissues and act on a diverse range of substrates. KLK-like enzyme activity has variously been reported to increase or decrease during the period leading up to ovulation in the equine chorionic gonadotrophin (eCG)primed, human chorionic gonadotrophin (hCG)-stimulated immature rat ovary. These earlier studies, which used biochemical assays to detect enzyme activity, lacked the specificity and sensitivity necessary to characterise conclusively the activity of the individual KLK gene family members. In this study, we have used a gene-specific RT-PCR/Southern hybridisation strategy to delineate the expression patterns of six of the individual KLK genes expressed in the rat ovary (rKLK1-3 and rKLK7-9). We have identified three broad patterns of expression in the eCG/hCG-stimulated ovary in which there is either a post-eCG increase/pre-ovulatory decrease in rKLK expression (rKLK1, rKLK3), a peri-ovulatory decrease in expression (rKLK2, rKLK8) or a relatively unchanged pattern of expression (rKLK7, rKLK9). In addition to clarifying the earlier biochemical studies, these findings support a differential role for the individual KLKs in the ovulatory process
Stage Door (1991) | Costume Sketch 007
No full textPerformed: 5-9 December 1991; George Kaufman\u27s Stage Door is a lighthearted comedy about a group of girls who go to New York to study acting and find jobs. The play was directed by Wayne Claeren, set by Carlton Ward, and costumes by Freddy Clements. Shown are costume sketches for Judith C., Susan Paige, Linda Shaw. This item is contained within the Clements drama production materials.https://digitalcommons.jsu.edu/clements_costumes/1095/thumbnail.jp
Stage Door (1991) | Costume Sketch 001
No full textPerformed: 5-9 December 1991; George Kaufman\u27s Stage Door is a lighthearted comedy about a group of girls who go to New York to study acting and find jobs. The play was directed by Wayne Claeren, set by Carlton Ward, and costumes by Freddy Clements. Shown are costume sketches for Judith C., Linda Shaw, and Kay Hamilton. This item is contained within the Clements drama production materials.https://digitalcommons.jsu.edu/clements_costumes/1089/thumbnail.jp
Kallikrein 4 (KLK4), A New Member of the Human Kallikrein Gene Family Is Up-Regulated By Estrogen and Progesterone in the Human Endometrial Cancer Cell Line, KLE
No full textEndometrial cancer is the fourth most common female malignancy in women in developed countries. Estrogen, and to a lesser degree, progesterone, regulate specific target genes that are involved in endometrial tumorigenesis. A family of proteases involved in cellular proliferation, extracellular matrix degradation and thus, implicated in tumorigenesis, and regulated by estrogen and progesterone in a number of systems, are the tissue kallikreins (KLKs). KLK4, a new member of the KLK gene family, was found to be expressed to varying levels in a number of endometrial cancer cell lines- HEC1A, HEC1B, Ishikawa, RL95-2 and KLE- at both the mRNA and protein level. On the addition of 10 nmol/L estradiol, progesterone, or a combination of both over a 48 h period, an increase in the intracellular protein levels of K4 were observed when compared to the control (untreated) cells. We have also identified a novel KLK4 transcript with a complete exon 4 deletion. The significance of this alternative transcript, which would give rise to a truncated protein without a serine residue (which is essential for catalytic activity), is yet to be established. These cell lines now provide a model system to study the role of KLK4 and the molecular mechanisms of KLK4 regulation by estrogen and progesterone, in endometrial tumorigenesis
Highlight: Proteolytic networks across cellular boundaries
No full textThe <i>9th General Meeting of the International Proteolysis Society (IPS)</i> was held in Penang, Malaysia, October 3–8, 2015. Each of our biennial IPS Meetings provides an excep - tional opportunity to bring together researchers from a wide variety of fields to provide educational, training, and networking opportunities at all levels, and to continue to forge international links between academic and indus - trial organisations with common interests in proteolysis. Over 150 scientists from the Americas, Europe, Africa, Asia, Australia and the Pacific region met to discuss the intricacies of proteolytic enzymes, their substrates, and inhibitors in health and disease. The International Advisory Committee was drawn from the international proteolysis research communities to ensure a breadth of expertise, insight into recent advances in the field and a high calibre program. A key feature of IPS 2015 was the inclusion of an Early Career Researcher Forum (organised by Sheena McGowan, Melbourne, Australia), which was attended by 40 young researchers. This included work - shops on Protease Kinetics, Imaging, Degradomics, and the Generation and Phenotypic Analysis of Genetically Modified Mice; rapid fire oral presentations by the young members-in-training; and an Industry vs. Academia work - shop led by Bob Lazarus, Genentech (IPS Council Presi- dent, 2013–2015)..
Reflections on the tissue kallikrein and kallikrein-related peptidase family - from mice to men - what have we learnt in the last two decades?
No full textThe genes encoding the kininogenase, glandular tissue kallikrein, in rodents and man were first described in the mid-1980s. Remarkably, they appeared to be part of a much larger highly conserved family of genes (GK) in rodents, but only had two paralogs in man. This discrepancy was not rectified until the late 1990s/2000 with the identification of a cluster of 12 more kallikrein-related (KLK) genes in the human 19q13 locus and the subsequent identification of their rodent homologs. Interestingly, there are remarkable similarities in expression patterns, hormonal regulation and functional attributes of the old (GK) and new (KLK) families which underscore the evolutionary conservation across these loci and species. This historical perspective focuses on the lessons learned from earlier studies on the rodent GK gene families and the striking similarities of some attributes, yet uniqueness, of others. These earlier findings have all contributed to the current status of the KLK serine peptidase-encoding gene family as an exciting source of new biomarkers and therapeutic target
Single nucleotide polymorphisms in clinics: Fantasy or reality for cancer?
No full textSingle nucleotide polymorphisms (SNPs) have been classically used for dissecting various human complex disorders using candidate gene studies. During the last decade, large scale SNP analysis i.e. genome-wide association studies (GWAS) have provided an agnostic approach to identify possible genetic loci associated with heterogeneous disease such as cancer susceptibility, prognosis of survival or drug response. Further, the advent of new technologies, including microarray based genotyping as well as high throughput next generation sequencing has opened new avenues for SNPs to be used in clinical practice. It is speculated that the utility of SNPs to understand the mechanisms, biology of variable drug response and ultimately treatment individualization based on the individual’s genome composition will be indispensable in the near future. In the current review, we discuss the advantages and disadvantages of the clinical utility of genetic variants in disease risk-prediction, prognosis, clinical outcome and pharmacogenomics. The lessons and challenges for the utility of SNP based biomarkers are also discussed, including the need for additional functional validation studies
Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model
No full textCell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. © 2010 Landes Bioscience
Kallikreins on steroids: structure, function and hormonal regulation of prostate-specific antigen and the extended kallikrein locus
No full textAbstractThe 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and putative proteolytic functions. The kallikrein family is also emerging as a rich source of disease biomarkers with KLK3, commonly known as prostate-specific antigen, being the current serum biomarker for prostate cancer. The kallikrein locus is also notable because it is extraordinarily responsive to steroids and other hormones. Indeed, at least 14 functional hormone response elements have been identified in the kallikrein locus. A more comprehensive understanding of the transcriptional regulation of kallikreins may help the field make more informed hypotheses about the physiological functions of kallikreins and their effectiveness as biomarkers. In this review, we describe the organization of the kallikrein locus and the structure of kallikrein genes and proteins. We also focus on the transcriptional regulation of kallikreins by androgens, progestins, glucocorticoids, mineralocorticoids, estrogens, and other hormones in animal models and human prostate, breast, and reproductive tract tissues. The interaction of the androgen receptor with androgen response elements in the promoter and enhancer of KLK2 and KLK3 is also summarized in detail. There is evidence that all kallikreins are regulated by multiple nuclear receptors. Yet, apart from KLK2 and KLK3, it is not clear whether all kallikreins are direct transcriptional targets. Therefore, we argue that gaining more detailed information about the mechanisms that regulate kallikrein expression should be a priority of future studies and that the kallikrein locus will continue to be an important model in the era of genome-wide analyses.</jats:p
A replication study examining novel common single nucleotide polymorphisms identified through a prostate cancer genome-wide association study in a Japanese population
No full textFive novel prostate cancer risk loci were identified in a recent genome-wide association study (GWAS) of Japanese persons (Takata et al., Nat Genet. 2010;42(9):751-754). Those authors proposed that apart from population-specific linkage disequilibrium patterns, limitations of GWAS single nucleotide polymorphism (SNP) prioritization and/or study design could explain the lack of identification of these loci in GWAS previously conducted among Caucasians. Thus, the authors undertook a replication study in 1,357 prostate cancer patients and 1,403 healthy Australian males of European descent (2004-2008). The rs12653946 SNP at 5p15 was found to be significantly associated with prostate cancer risk (odds ratio = 1.20, 95% confidence interval: 1.07, 1.34; P = 0.002). On the basis of linkage disequilibrium calculations, the rs12653946 SNP represents an independent locus, distinct from the previously identified TERT-CLPTM1L cancer nexus region. Further, analysis from AceView (Thierry-Mieg and Thierry-Mieg, Genome Biol. 2006;7(suppl 1):S12) indicated that rs12653946 falls within the intron of a testis-expressed gene strongly predicted to translate a conceptual 8.1-kilodalton protein named tojy.aApr07. The authors' findings suggest that follow-up of apparently ethnicity-specific risk associations are warranted in order to highlight risk-associated loci for experimental studies and for incorporation into future risk prediction models for prostate cancer. American Journal of Epidemiology © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected] © American Journal of Epidemiology © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected]
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