RT Journal
A1 Mazzanti, Chiara M.
A1 Tandle, Anita
A1 Lorang, Dominique
A1 Costouros, Nick
A1 Roberts, David
A1 Bevilacqua, Generoso
A1 Libutti, Steven K.
T1 Early Genetic Mechanisms Underlying the Inhibitory Effects of Endostatin and Fumagillin on Human Endothelial Cells
JF Genome Research 
JO Genome Research 
YR 2004 
FD August 01 
VO 14 
IS 8 
SP 1585 
OP 1593 
DO 10.1101/gr.2552804 
UL http://genome.cshlp.org/content/14/8/1585.abstract 
AB A tumor needs to initiate angiogenesis in order to develop its own blood supply, to grow, to invade, and to spread. Angiogenesis, under normal conditions, is a tightly regulated balance between endogenous pro- and antiangiogenic factors. In this study, we investigated, by microarray analysis, the effects of two known antiangiogenic agents (endostatin and fumagillin) on the gene expression profiles of human umbilical vein endothelial cells (HUVEC) in order to elucidate pathways common to the effects of these agents. We observed a majority of gene expression changes within 1 and 2 h of treatment. The genes demonstrating these early expression changes are involved in cell proliferation, gene transcription, and a number have unknown functions. We selected four genes (DOC1, KLF4, TC-1, ID1) from the microarray profile that showed a similar pattern of expression for both of the antiangiogenic agents we tested. We then used small interfering RNAs (siRNA) in an attempt to better understand the role of these selected genes in the inhibitory activity of these agents. Because the gene expression changes occurred within 1 and 2 h of treatment, these genes might be involved in the initial pathways of angiogenesis inhibition.