Yousef G M, Luo L Y, Diamandis E P
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Anticancer Res. 1999 Jul-Aug;19(4B):2843-52.
The human kallikrein gene family is localized on chromosome 19q13.3-q13.4 and currently includes three members: KLK1 or pancreatic/renal kallikrein, KLK2 or human glandular kallikrein and KLK3 or prostate-specific antigen (PSA). The latter two genes are almost prostate-specific and they are used for diagnosis and monitoring of prostate cancer and more recently, in breast cancer applications. In this paper, we analyzed a 300Kb genomic DNA region around chromosome 19q13.3-q13.4 in an effort to map known kallikrein or kallikrein-like genes and identify new kallikrein-like genes. Using the known kallikrein or kallikrein-like genes PSA, KLK2, enzyme and normal epithelial cell-specific 1 gene (NES1) as landmarks, we have identified another six novel genes of which, five have protein homologies and gene structure similarities with other kallikreins or kallikrein-like genes. We conclude, contrary to the current belief, that the human kallikrein gene locus contains a large number of kallikrein-like genes (at least thirteen). In this paper, we present a detailed description of the human kallikrein gene locus, encompassing the already known and newly identified genes. These new genes, like the already known kallikreins, may have utility for diagnosis, monitoring and therapeutics of various cancers including those of the breast, prostate and testis.
人类激肽释放酶基因家族定位于19号染色体的19q13.3 - q13.4区域,目前包括三个成员:KLK1即胰/肾激肽释放酶、KLK2即人腺体激肽释放酶以及KLK3即前列腺特异性抗原(PSA)。后两个基因几乎是前列腺特异性的,它们被用于前列腺癌的诊断和监测,最近也用于乳腺癌相关应用。在本文中,我们分析了19号染色体19q13.3 - q13.4周围一个300Kb的基因组DNA区域,旨在定位已知的激肽释放酶或类激肽释放酶基因,并鉴定新的类激肽释放酶基因。以已知的激肽释放酶或类激肽释放酶基因PSA、KLK2、酶和正常上皮细胞特异性1基因(NES1)作为标记,我们鉴定出另外六个新基因,其中五个与其他激肽释放酶或类激肽释放酶基因具有蛋白质同源性和基因结构相似性。我们得出结论,与当前的认知相反,人类激肽释放酶基因座包含大量类激肽释放酶基因(至少十三个)。在本文中,我们详细描述了人类激肽释放酶基因座,包括已知名的和新鉴定出的基因。这些新基因与已知名的激肽释放酶一样,可能对包括乳腺癌、前列腺癌和睾丸癌在内的各种癌症的诊断、监测和治疗具有实用价值。