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Identification of a Novel Complex between Human Kallikrein 2 and Protease Inhibitor-6 in Prostate Cancer Tissue

Hybritech Inc., San Diego, California 92121 [S. D. M., L. S. Mi., K. M. M., H. G. R., R. L. W.]; University of California at Los Angeles, Los Angeles, California 90095 [L. S. Ma.]; and Mayo Clinic, Rochester, Minnesota 55905 [M. C. C., D. J. T.]

Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate that has an 80% sequence identity with prostate-specific antigen. Expression of hK2 is elevated in the tumor epithelium compared to benign prostate tissue. We have purified, sequenced, and identified a novel hK2 complex in prostate tissue consisting of hK2 and a serine protease inhibitor known as protease inhibitor-6 (PI-6). This 64-kDa SDS-PAGE stable complex is elevated in the tumor and is approximately 10% of total hK2. No comparable complex of prostate-specific antigen was detected. PI-6, also known as cytoplasmic antiprotease, has been characterized as an intracellular inhibitor of trypsin and chymotrypsin-like proteases, which has high homology to plasminogen activator inhibitor 1 and 2. The physiological role of PI-6 in the prostate and its relationship to hK2 and prostate cancer are under investigation.

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