TY - JOUR
T1 - RUNX3 inhibits the expression of vascular endothelial growth factor and reduces the angiogenesis, growth, and metastasis of human gastric cancer
AU - Peng, Zhihai
AU - Wei, Daoyan
AU - Wang, Liwei
AU - Tang, Huamei
AU - Zhang, Jun
AU - Le, Xiangdong
AU - Jia, Zhiliang
AU - Li, Qiang
AU - Xie, Keping
PY - 2006/11/1
Y1 - 2006/11/1
N2 - Purpose: Recent studies indicated that RUNX3 exhibits potent antitumor activity. However, the underlying molecular mechanisms of this activity remain unclear. In the present study, we used a gastric cancer model to determine the effect of RUNX3 expression on tumor angiogenesis. Experimental Design: The effects of increased RUNX3 expression on vascular endothelial growth factor (VEGF) expression in and angiogenic potential of human gastric cancer cells were determined in vitro and in animal models. RUNX3 and VEGF expression was determined in 120 human gastric cancer specimens and their relationship was analyzed. Results: RUNX3 gene transfer suppressed VEGF expression in human gastric cancer cells. Down-regulation of VEGF expression correlated with a significantly impaired angiogenic potential of human gastric cancer cells. Furthermore, RUNX3 restoration inhibited tumor growth and metastasis in animal models, which was consistent with inhibition of angiogenesis as determined by evaluating VEGF expression and tumor microvessel formation. In gastric cancer specimens, loss or decrease in RUNX3 expression inversely associated with increased VEGF expression and elevated microvessel formation. Conclusions: Our clinical and experimental data provide a novel molecular mechanism for the antitumor activity of RUNX3 and may help design effective therapy targeting RUNX3 pathway to control gastric cancer growth and metastasis.
AB - Purpose: Recent studies indicated that RUNX3 exhibits potent antitumor activity. However, the underlying molecular mechanisms of this activity remain unclear. In the present study, we used a gastric cancer model to determine the effect of RUNX3 expression on tumor angiogenesis. Experimental Design: The effects of increased RUNX3 expression on vascular endothelial growth factor (VEGF) expression in and angiogenic potential of human gastric cancer cells were determined in vitro and in animal models. RUNX3 and VEGF expression was determined in 120 human gastric cancer specimens and their relationship was analyzed. Results: RUNX3 gene transfer suppressed VEGF expression in human gastric cancer cells. Down-regulation of VEGF expression correlated with a significantly impaired angiogenic potential of human gastric cancer cells. Furthermore, RUNX3 restoration inhibited tumor growth and metastasis in animal models, which was consistent with inhibition of angiogenesis as determined by evaluating VEGF expression and tumor microvessel formation. In gastric cancer specimens, loss or decrease in RUNX3 expression inversely associated with increased VEGF expression and elevated microvessel formation. Conclusions: Our clinical and experimental data provide a novel molecular mechanism for the antitumor activity of RUNX3 and may help design effective therapy targeting RUNX3 pathway to control gastric cancer growth and metastasis.
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U2 - 10.1158/1078-0432.CCR-05-2359
DO - 10.1158/1078-0432.CCR-05-2359
M3 - Article
C2 - 17085650
AN - SCOPUS:33751266107
SN - 1078-0432
VL - 12
SP - 6386
EP - 6394
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -