Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells

Johanna M. Mattsson, Pirjo Laakkonen, Sami Kilpinen, Ulf-Håkan Stenman, Hannu Koistinen

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)765-771
JournalBiological Chemistry
Volume389
Issue number6
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Kallikreins
Endothelial cells
Human Umbilical Vein Endothelial Cells
Gene expression
Peptide Hydrolases
Gene Expression
Proteolysis
Focal Adhesions
Chymotrypsin
Enzyme activity
Proteasome Endopeptidase Complex
Prostate-Specific Antigen
Microarrays
Ubiquitin
Oligonucleotide Array Sequence Analysis
Actin Cytoskeleton
Actins
Adhesion
Genes
Cells

Keywords

  • angiogenesis
  • cell culture
  • microarray
  • prostate cancer
  • PSA

Cite this

Mattsson, Johanna M. ; Laakkonen, Pirjo ; Kilpinen, Sami ; Stenman, Ulf-Håkan ; Koistinen, Hannu. / Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells. In: Biological Chemistry. 2008 ; Vol. 389, No. 6. pp. 765-771.
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Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells. / Mattsson, Johanna M.; Laakkonen, Pirjo; Kilpinen, Sami; Stenman, Ulf-Håkan; Koistinen, Hannu.

In: Biological Chemistry, Vol. 389, No. 6, 2008, p. 765-771.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

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AU - Mattsson, Johanna M.

AU - Laakkonen, Pirjo

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AU - Stenman, Ulf-Håkan

AU - Koistinen, Hannu

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AB - 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.

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