题名：Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis
作者：Jide Wang, Yi Yang, Harry H.X. Xia, Qing Gu, Marie C.M. Lin, Bo Jiang, Ying Peng, Guoqing Li, Xiaomeng An, Yali Zhang, et al.
来源：Gastroenterology[IF=12.386], Volume 132, Issue 3, March 2007, Pages 1066-1076
摘要： Jide Wang, ?, Yi Yang?, Harry H.X. Xia?, Qing Gu?, Marie C.M. Lin, Bo Jiang, Ying Peng, Guoqing Li?, Xiaomeng An, Yali Zhang, Zehao Zhuang?, Zhenshu Zhang, Hsiang Fu Kung? and Benjamin C.Y. Wong?, ,
?Department of Medicine, University of Hong Kong, Hong Kong
Institute for Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Peoples Republic of China
Department of Neurology, Second Affliated Hospital, Sun Yat-Sen University, Peoples Republic of China
Department of Chemistry, University of Hong Kong, Hong Kong
?The Center for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
Received 4 March 2006; accepted 16 November 2006. Available online 3 December 2006.
Background & Aims: FHL2 (4-1/2 LIM protein 2) is an adapter and modifier in protein interactions that is expressed mainly in the heart and ovary. It functions in a cell type- or promoter-specific manner. The aims of this study were to examine its expression in gastrointestinal cancers and to determine its role in cell differentiation and tumorigenesis. Methods: FHL2 expression in cancerous and normal gastrointestinal cells was detected by reverse-transcription polymerase chain reaction, immunoblotting, and immunohistochemistry. The effect of FHL2 suppression by both antisense and siRNA methods on cell differentiation and growth were evaluated in vitro and in vivo. Results: FHL2 expression was up-regulated in gastrointestinal cancer, compared with matched normal tissues. Stable transfection of gastric cancer cell line, AGS, and colon cancer cell line, Lovo, with antisense FHL2 induced lengthened or shuttle-shape morphologic changes with long or dendritic-like cytoplasmic processes and decreased the nuclear:cytoplasmic ratio. FHL2 antisense induced expressions of carinoembryonic antigen and E-cadherin and the maturation of F-actin. Furthermore, FHL2 antisense inhibited the transcriptions of some oncogenes including cox-2, survivin, c-jun, and hTERT, and suppressed the promoter activity of activator protein-1 and hTERT. Suppression of FHL2 inhibited serum-dependent, anchorage-dependent and -independent cell growth, and suppressed de novo tumor formation in nude mice xenograft. Conclusions: Suppression of FHL2 induces cell differentiation and inhibits tumorigenesis. Antisense or siRNA methods targeting FHL2 is a promising strategy for treatment of gastrointestinal cancers. 18.