MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

被引:41
作者
Hsu, Kai-Wen [1 ,2 ]
Hsieh, Rong-Hong [3 ]
Wu, Chew-Wun [4 ,5 ]
Chi, Chin-Wen [6 ,8 ]
Lee, Yan-Hwa Wu [7 ]
Kuo, Min-Liang [9 ,10 ]
Wu, Kou-Juey [7 ]
Yeh, Tien-Shun [1 ,2 ]
机构
[1] Natl Yang Ming Univ, Dept Anat & Cell Biol, Taipei 112, Taiwan
[2] Taipei Med Univ, Grad Inst Med Sci, Taipei, Taiwan
[3] Taipei Med Univ, Grad Inst Nutr & Hlth Sci, Taipei, Taiwan
[4] Taipei Vet Gen Hosp, Dept Surg, Taipei, Taiwan
[5] Natl Yang Ming Univ, Dept Surg, Taipei 112, Taiwan
[6] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan
[7] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan
[8] Natl Yang Ming Univ, Dept & Inst Pharmacol, Taipei 112, Taiwan
[9] Natl Taiwan Univ, Lab Mol & Cellular Toxicol, Inst Toxicol, Coll Med, Taipei 10764, Taiwan
[10] Natl Taiwan Univ, Angiogenesis Res Ctr, Taipei 10764, Taiwan
关键词
C-MYC PROMOTER; BINDING-PROTEIN MBP-1; TRANSCRIPTION FACTOR YY1; ALPHA-ENOLASE; CYCLOOXYGENASE-2; PROTEIN; MESENCHYMAL TRANSITIONS; INCREASED EXPRESSION; SIGNAL PATHWAY; LUNG-CANCER; NUDE-MICE;
D O I
10.1091/mbc.E09-05-0386
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1-suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.
引用
收藏
页码:5127 / 5137
页数:11
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