MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2.
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.
Hsu
Kai-Wen
KW
Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
Hsieh
Rong-Hong
RH
Wu
Chew-Wun
CW
Chi
Chin-Wen
CW
Lee
Yan-Hwa Wu
YH
Kuo
Min-Liang
ML
Wu
Kou-Juey
KJ
Yeh
Tien-Shun
TS
D000596:Amino Acids / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D013329:Structure-Activity Relationship
D000596:Amino Acids; C088830:DENND4A protein, human; D004268:DNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human