Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 765-771 |
| Journal | Biological Chemistry |
| Volume | 389 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2008 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- angiogenesis
- cell culture
- microarray
- prostate cancer
- PSA
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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 journal › Article › Scientific › peer-review
TY - JOUR
T1 - Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
AU - Mattsson, Johanna M.
AU - Laakkonen, Pirjo
AU - Kilpinen, Sami
AU - Stenman, Ulf-Håkan
AU - Koistinen, Hannu
PY - 2008
Y1 - 2008
N2 - 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.
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.
KW - angiogenesis
KW - cell culture
KW - microarray
KW - prostate cancer
KW - PSA
U2 - 10.1515/BC.2008.088
DO - 10.1515/BC.2008.088
M3 - Article
VL - 389
SP - 765
EP - 771
JO - Biological Chemistry
JF - Biological Chemistry
SN - 1431-6730
IS - 6
ER -