Gastric Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2008; 14(16): 2487-2493
Published online Apr 28, 2008. doi: 10.3748/wjg.14.2487
Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells
Geng-Qiu Luo, Jing-He Li, Ji-Fang Wen, Yan-Hong Zhou, Yong-Bin Hu, Jian-Hua Zhou
Geng-Qiu Luo, Jing-He Li, Ji-Fang Wen, Yong-Bin Hu, Jian-Hua Zhou, Department of Pathology, Basic School of Medicine, Central South University, Changsha 410008, Hunan Province, China
Yan-Hong Zhou, Institute of Cancer Research, Xiangya School of Medicine, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Luo GQ wrote the paper and organized the figures and experiment data; Wen JF and Li JH designed the research; Zhou YH carried out the statistical analysis; Hu YB and Zhou JH helped wrote, organized and corrected the paper.
Correspondence to: Dr. Ji-Fang Wen, Department of Pathology, Basic School of Medicine, Central South University, Changsha 410008, Hunan Province, China. jifangwen@hotmail.com
Telephone: +86-731-2355098
Fax: +86-731-2650400
Received: November 10, 2007
Revised: January 14, 2008
Published online: April 28, 2008
Abstract

AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved.

METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method.

RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS-MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased.

CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/Tcf-4 signaling.

Keywords: Twist, Gastric carcinoma, Cancer invasion, Metastasis, Tcf4