The balance between two isoforms of LEF-1 regulates colon carcinoma growth

BMC Gastroenterology

Research Article

Yao-Chun Wang¹  Ke-Jun Nan²  Tao Tian²  Wen-Juan Wang²  Shu-Hong Wang² 

[1] Center for Cell-Biological Therapy and Research, General Hospital of Guangzhou Millitary Command of PLA, Guangzhou, Guangdong Province, P.R. China;Department of Medical Oncology, The First Affiliated Hospital of the School of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P.R. China;

关键词: HT29 Cell;    SW480 Cell;    Colon Cell;    Colon Cancer Cell Line;    Colon Cell Line;   

DOI  :  10.1186/1471-230X-12-53

 received in 2011-03-30, accepted in 2012-05-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundColon cancer is one of the most aggressive human malignancies, with a very poor prognosis. Although it has been suggested that different isoforms of the lymphoid enhancer factor (LEF-1) have opposing biological activities, the biological outcome of aberrant LEF-1 activation in colon cancer is still unclear. The aim of this study was to evaluate the effect of the different LEF-1 phenotypes on the growth of colon carcinoma cell lines. A deeper understanding of these processes might improve the targeted therapies for colon cancer by regulating the expression of LEF-1.MethodsThe role of different isoforms of LEF-1 on the growth of human colon carcinoma cell lines (SW480 and HT-29) was studied using various in vitro and in vivo assays. In vitro proliferation, migration, adhesion and apoptosis of the cells stably transfected of different isoforms of LEF-1 were monitored by MTT assay, carboxyfluorescein diacetate–succinimidyl ester staining, annexin V staining, ECM adhesion assay and transwell assay, respectively. In nude mice, the formation of neovasculature in the tumors formed by our constructed cells was measured by immunohistochemistry. All the data were analyzed using a t test, and data were treated as significant when p < 0.05.ResultsOverexpression of truncated LEF-1 (LEF-1-ΔL) in the colon cell lines, SW480 and HT29, inhibited their growth significantly in vitro and in vivo, but the full-length LEF-1 (LEF-1-FL) promoted the proliferation of HT29. Inactivation of Wnt signaling by LEF-1-ΔL reduced the expression of CXCR4 in colon cell lines, which may lead to a decrease in activities such as migration, adhesion and survival. In nude mice, the formation of neovasculature as well as an increase in tumor volume were inhibited by the short isoform of LEF-1. LEF-1-FL, however, caused an increase in all these parameters compared with controls.ConclusionsThese findings suggest that LEF-1 might play an important role in colon carcinogenesis by acting as a regulator. Enhanced expression of LEF-1-FL, which occurs frequently in colon cancer, may be a new target for clinical therapy.

【 授权许可】

CC BY   
© Wang et al.; licensee BioMed Central Ltd. 2012