The new human kallikrein gene family: Implications in carcinogenesis

The traditional human kallikrein gene family consists of three genes, namel y KLK1 [encoding human kallikrein 1 (hK1) or pancreatic/renal kallikrein], KLK2 ( encoding hK2, previously known as human glandular kallikrein 1) and KLK3 [encoding hK3 or prostate-specific antigen (PSA)]. KLK2 and KLK3 have important applications in prostate cancer diagnostics and, more recently in breast cancer diagnostic. During the past two or three years, new putative members of the human kallikrein gene family have been identified, includin g the PRSSL1 gene [ encoding normal epithelial cell-specific 1 gene (NES1)] , the gene encoding zyme/protease M/neuropsin, the gene encoding protese/KL K-L1, and the encoding neuropsin, stratum corneum chymotryptic enzyme and t rypsin-like serine protease. Another five putative kallikrein genes, provis ionally named KLK-L2, KLK-L3, KLK-L4, KLK-L4, KLK-L5 and KLK-L6, have also been identified. Many if the newly identified kallikrein-like genes are reg ulated by steroid hormones, and a few kallikreins (NES1, protease M, PSA) a re known to be downregulated in breast and possibly other cancers. NES1 app ears to be a novel breast cancer tumor suppressor protein and psa a potent inhibitor of angiogenesis. This brief review summarizes recent developments and possible applications of the newly defined and expanded human kallikre in gene locus.