Gastric Cancer
Copyright ©The Author(s) 2002. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2002; 8(3): 446-450
Published online Jun 15, 2002. doi: 10.3748/wjg.v8.i3.446
Induction of apoptosis by TPA and VP-16 is through translocation of TR3
Su Liu, Qiao Wu, Xiao-Feng Ye, Jian-Huai Cai, Zhi-Wei Huang, Wen-Jin Su
Su Liu, Qiao Wu, Xiao-Feng Ye, Jian-Huai Cai, Zhi-Wei Huang, Wen-Jin Su, Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Outstanding Youth Science foundation of China (B type, 39825502); the National Natural Science Foundation of China (39880015, 30170477); the Natural Science Foundation of Fujian Province (C0110004).
Correspondence to: Dr. Qiao Wu, Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian Province, China. xgwu@xmu.edu.cn
Telephone: +86-592-2182542 Fax: +86-592-2086630
Received: November 2, 2001
Revised: November 23, 2001
Accepted: December 20, 2001
Published online: June 15, 2002
Abstract

AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells.

METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot and Western blot. Localization of TR3 protein was showed by immunofluorescence analysis under laser-scanning confocal microscope. Apoptotic morphology was observed by DAPI fluorescence staining, and apoptotic index was counted among 1000 cells randomly. Stable transfection assay was carried out by Lipofectamine.

RESULTS: Treatment of MGC80-3 cells with TPA and VP-16 resulted in apoptosis, accompanied by the repression of Bcl-2 protein in a time-dependent manner. At the same time, TPA and VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that expressed TR3 mRNA. When antisense-TR3 expression vector was transfected into the cells, expression of TR3 protein was repressed. In this case, TPA and VP-16 did not induce apoptosis. In addition, TPA and VP-16-induced apoptosis involved in translocation of TR3. In MGC80-3 cells, TR3 localized concentrative in nucleus, after treatment of cells with TPA and VP-16, TR3 translocated from nucleus to cytosol obviously. However, when this nuclear translocation was blocked by LMB, apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP-16.

CONCLUSION: Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation of TR3 from nucleus to cytosol, which may be a novel signal pathway for TR3, and represent the new biological function of TR3 to exert its effect on apoptosis in gastric cancer cells.

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