Johanna M. Mattsson, 11Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 University of Helsinki, Finland
Pirjo Laakkonen, 22Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, 00014 University of Helsinki, Finland
Sami Kilpinen, 33Medical Biotechnology, VTT Technical Research Center and University of Turku, 20520 Turku, Finland, and Genome-Scale Biology Research Program, Biomedicum Helsinki, 00014 University of Helsinki, Finland
Ulf-Håkan Stenman, 44Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 University of Helsinki, Finland
Hannu Koistinen, 55Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 University of Helsinki, Finland
Corresponding author
Citation Information. Biological Chemistry. Volume 389, Issue 6, Pages 765–771, ISSN (Online) 14374315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.088, June 2008
Publication History: Received: 14/12/2007; accepted: 10/3/2008; published online: 15/05/2008
Abstract
Kallikrein-related peptidase 3 (KLK3, also known as prostate-specific antigen, PSA) is a chymotrypsin-like kallikrein that has anti-angiogenic properties. We have previously shown in a human umbilical vein endothelial cell (HUVEC) model that the anti-angiogenic effect of KLK3 is related to its enzyme activity. However, the mechanism of this effect remains to be clarified. To this end, we used a DNA microarray to study KLK3-induced changes in gene expression associated with reduction of HUVEC tube formation. Among the 41 000 genes studied, 311 were differentially expressed between control and KLK3-treated cells. These changes were enriched in several pathways, including those associated with proteasome, ubiquitin-mediated proteolysis, focal adhesion and regulation of the actin cytoskeleton. Furthermore, the changes were opposite to those previously described to occur during tubulogenesis. In conclusion, our results show that KLK3 induces gene expression changes in HUVECs. Although these changes might be relevant for the mechanism by which KLK3 exerts its anti-angiogenic activity, it cannot be judged from the present results whether they reflect the primary mechanism mediating the effect of KLK3 or are secondary to morphogenic differentiation.
Keywords angiogenesis, cell culture, microarray, prostate cancer, PSA
