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 func- tions 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 gastroin- testinal cells was detected by reverse-transcription polymerase chain reaction, immunoblotting, and im- munohistochemistry. The effect of FHL2 suppression by both antisense and siRNA methods on cell differ- entiation and growth were evaluated in vitro and in vivo. Results: FHL2 expression was up-regulated in gastrointestinal cancer, compared with matched nor- mal tissues. Stable transfection of gastric cancer cell line, AGS, and colon cancer cell line, Lovo, with an- tisense FHL2 induced lengthened or shuttle-shape morphologic changes with long or dendritic-like cy- toplasmic processes and decreased the nuclear:cyto- plasmic 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 in- cluding cox-2, survivin, c-jun, and hTERT, and sup- pressed 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 tu- morigenesis. Antisense or siRNA methods targeting FHL2 is a promising strategy for treatment of gastro- intestinal cancers.

第一署名医院：南方医科大学南方医院