Human tissue kallikreins: from gene structure to function and clinical applications.

Publisher Summary Kallikreins are expressed in many organs, most prominently in endocrine-related tissues such as the prostate, breast, ovary, uterus, vagina, and testis. The coexpression of many kallikreins in several cancer types and other information pointing to the possibility of their involvement in a cascade-like pathway that may be associated with cancer pathogenesis or progression are presented in this chapter. Characterization and sequence analysis of human-tissue kallikrein gene locus are discussed in this chapter. A short historical perspective of the discovery of human-tissue kallikrein gene locus is presented in this chapter. Kallikreins in rodents and other species such as the mouse kallikrein gene family, the rat kallikrein gene family, and the dog kallikrein gene family are also described in this chapter. Structural features of human-tissue kallikrein genes and proteins such as common structural features and three-dimensional structure are also presented in this chapter. Sequence variations of human kallikrein genes, the tissue kallikreins in the context of other serine proteases in the human genome, tissue expression and cellular localization of the kallikrein genes, regulation of kallikrein activity (at the mRNA level, at the protein level, locus control of kallikrein expression, and epigenetic regulation of kallikrein gene expression), hormonal regulation of kallikreins, and evolution of kallikreins are also presented in this chapter. Prognostic and predictive value of kallikreins in hormone-dependent cancers such as ovarian cancer, breast cancer, and prostate cancer is also described in this chapter. The enzymatic activity of these serine proteases may initiate or terminate biological events. A third possible therapeutic approach involves immunotherapy or development of cancer vaccines. With increasing knowledge of the hormonal regulation of kallikreins, hormonal activation (or repression) of kallikrein activity could be investigated in the future.