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Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus Lawrence MG; Lai J; Clements JAEndocr Rev 2010[Aug]; 31 (4): 407-46The 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.|*Hormones/pharmacology[MESH]|*Kallikreins/chemistry/genetics/physiology[MESH]|*Prostate-Specific Antigen/chemistry/genetics/physiology[MESH]|Androgens/pharmacology[MESH]|Animals[MESH]|Biomarkers, Tumor/blood[MESH]|Breast/chemistry[MESH]|Chromosomes, Human, Pair 19[MESH]|Estrogens/pharmacology[MESH]|Evolution, Molecular[MESH]|Female[MESH]|Gene Expression Regulation/drug effects[MESH]|Genetic Loci/genetics[MESH]|Glucocorticoids/pharmacology[MESH]|Humans[MESH]|Male[MESH]|Mineralocorticoids[MESH]|Models, Molecular[MESH]|Molecular Structure[MESH]|Polymorphism, Genetic[MESH]|Progestins/pharmacology[MESH]|Promoter Regions, Genetic/genetics[MESH]|Prostate/chemistry[MESH]|Prostatic Neoplasms/blood[MESH] |
