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Cloning of a New Member of the Human Kallikrein Gene Family, KLK14, Which Is Down-Regulated in Different Malignancies

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [G. M. Y., A. M., A. C., E. P. D.]; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5G 1LS, Canada [G. M. Y., A. M., A. C., E. P. D.]; Department of Urology, University Hospital Charite, Humboldt University, Berlin D-10098, Germany [K. J.]; and Department of Gynecologic Oncology, Institute of Obstetrics and Gynecology, University of Turin, Turin 10128, Italy [D. K.]

Kallikreins (KLKs) belong to the serine protease family of proteolytic enzymes. Human pancreatic/renal KLK (KLK1) encodes for an enzyme that is involved in posttranslational processing of polypeptide precursors. The function of the other members of this gene family is currently unknown, but growing evidence suggests that many KLKs are implicated in carcinogenesis. By using the positional candidate approach, we were able to identify a new human KLK-like gene, KLK14 (also known as KLK-L6). This new gene maps to chromosome 19q13.3–q13.4 and is formed of seven exons (two untranslated and five coding exons) and six intervening introns. KLK14 was defined as a KLK gene based on structural and mapping criteria, in relation to other known KLK genes. KLK14 is expressed in a variety of tissues, but the highest levels of KLK14 are found in the central nervous system, including brain, cerebellum, and spinal cord. Our preliminary results show that KLK14 is down-regulated, at the mRNA level, in breast, testicular, prostatic, and ovarian cancer.

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