Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding 
protein belonging to the multigenic S100 family. In high-grade ductal carcinoma 
in situ, psoriasin was identified as one of the most abundant transcripts. We 
have previously shown that psoriasin was induced by reactive oxygen species 
(ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) 
led to the reduced expression of vascular endothelial growth factor (VEGF) and 
inhibited tumor growth in vivo. The aim of the present study was to investigate 
whether psoriasin could have direct effects on endothelial cells. In this study 
we demonstrated that psoriasin increased VEGF expression in mammary epithelial 
cells. The treatment of endothelial cells with recombinant psoriasin increased 
proliferation comparable to that of recombinant VEGF protein. No change in 
proliferation was seen when endothelial cells were infected with 
psoriasin-expressing adenoviruses, suggesting that the proliferative effect of 
psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting 
the receptor for advanced glycation end products (RAGE), thus inhibited 
endothelial cell proliferation and tube formation enhanced by recombinant 
psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, 
when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin 
induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and 
epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation 
of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein 
abolished the effect of psoriasin on endothelial cell proliferation. Our data 
suggest that psoriasin expression in mammary epithelial cells leads to increased 
endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may 
therefore play a role in breast cancer progression by promoting oxidative stress 
response and angiogenesis.