TY - JOUR
T1 - Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis
AU - Wei, Daoyan
AU - Gong, Weida
AU - Oh, Sang C.
AU - Li, Qiang
AU - Kim, Won Dong
AU - Wang, Liwei
AU - Le, Xiangdong
AU - Yao, James
AU - Wu, Tsung T.
AU - Huang, Suyun
AU - Xie, Keping
PY - 2005/6/1
Y1 - 2005/6/1
N2 - Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P < 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin Dl but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer
AB - Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P < 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin Dl but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer
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U2 - 10.1158/0008-5472.CAN-04-3741
DO - 10.1158/0008-5472.CAN-04-3741
M3 - Article
C2 - 15930301
AN - SCOPUS:21144440536
SN - 0008-5472
VL - 65
SP - 4809
EP - 4816
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -