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World J Gastroenterol. Mar 7, 2008; 14(9): 1437-1443
Published online Mar 7, 2008. doi: 10.3748/wjg.14.1437
Activator protein-1 involved in growth inhibition by RASSF1A gene in the human gastric carcinoma cell line SGC7901
Zheng-Hao Deng, Ji-Fang Wen, Jing-He Li, De-Sheng Xiao, Jian-Hua Zhou
Zheng-Hao Deng, Ji-Fang Wen, Jing-He Li, De-Sheng Xiao, Jian-Hua Zhou, Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan Province, China
Author contributions: Deng ZH experiment design, gene transfection, tumorigenicity in nude mice and manuscript writing; Wen JF corrected the manuscript; Li JH analysed Western blot and RT-PCR; did cell culture, analysed cytobiology and EMSA; the statistical tests were carried out by Zhou JH.
Correspondence to: Professor Ji-Fang Wen, Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan Province, China. jifangwen@hotmail.com
Telephone: +86-731-2650400
Fax: +86-731-2650400
Received: August 30, 2007
Revised: November 13, 2007
Published online: March 7, 2008
Abstract

AIM: To investigate the role of Ras association domain family protein 1 isoform A (RASSF1A) in gastric tumorigenesis.

METHODS: Through over-expression of RASSF1A gene in the SGC7901 cell line which was induced by a lipofectamine-mediated gene transfer approach. Activator protein-1 (AP-1) DNA binding activity was measured by electrophoretic mobility shift assay (EMSA).

RESULTS: Compared with the control clones, cells over-expressing RASSF1A exhibited significant inhibition of cell growth with G1 cell cycle arrest in vitro and in vivo. The over-expression of RASSF1A significantly inhibited AP-1 activity in SGC7901 cells (0.981 ± 0.011 vs 0.354 ± 0.053, P < 0.001). In addition, both Western blot analysis and immunocytochemistry demonstrated that RASSF1A down-regulated the expression of c-Fos (0.975 ± 0.02 vs 0.095 ± 0.024, P < 0.001) but not c-Jun.

CONCLUSION: Over-expression of RASSF1A inhibits the growth of SGC7901 cells by negatively regulating the AP-1 activity, the latter in turn negatively signals cell proliferation.

Keywords: RASSF1A, Gastric adenocarcinoma, SGC7901, Activator protein-1