The balance between two isoforms of LEF-1 regulates colon carcinoma growth.
The balance between two isoforms of LEF-1 regulates colon carcinoma growth.
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LEF-1 两种异构体之间的平衡调节结肠癌生长
DOI：
10.1186/1471-230x-12-53
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发表时间：
2012-05-28
影响因子：
2.4
通讯作者：
Tian T
中科院分区：
文献类型：
--
作者：
Wang SH;Nan KJ;Wang YC;Wang WJ;Tian T
结肠癌是最具侵袭性的人类恶性肿瘤之一，预后非常差。尽管有研究表明，不同亚型的淋巴细胞增强因子（LEF-1）具有相反的生物学活性，但LEF-1异常活化在结肠癌中的生物学结果尚不清楚。本研究的目的是评估不同的LEF-1表型对结肠癌细胞系生长的影响。对这些过程的深入了解可能会通过调节LEF-1的表达来改善结肠癌的靶向治疗。方法采用多种体外和体内实验方法，研究不同亚型的LEF-1对人结肠癌细胞株SW480和HT-29生长的影响。分别用MTT法、羧基荧光素二乙酸-琥珀酰亚胺酯染色法、膜联蛋白V染色法、ECM粘附法和transwell法检测稳定转染不同亚型LEF-1的细胞的体外增殖、迁移、粘附和凋亡情况。在裸鼠中，用免疫组织化学方法检测了我们构建的细胞形成的肿瘤中新生血管的形成。所有数据采用检验方法进行分析，以p < 0.05为显著。结果在结肠细胞系SW480和HT29中，过表达截断的lev -1 （lev -1-ΔL）在体外和体内均能显著抑制其生长，而全长的lev -1 （lev -1- fl）则能促进HT29的增殖。通过LEF-1-ΔL使Wnt信号失活，降低了结肠细胞系中CXCR4的表达，这可能导致其迁移、粘附和存活等活性的降低。在裸鼠中，LEF-1短异构体抑制了新生血管的形成和肿瘤体积的增加。然而，与对照组相比，LEF-1-FL引起所有这些参数的增加。结论提示LEF-1可能作为调节因子在结肠癌发生过程中发挥重要作用。结肠癌中常见的LEF-1-FL表达增强可能成为临床治疗的新靶点。
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 variousin vitroandin vivoassays.In vitroproliferation, 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 attest, 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 significantlyin vitroandin 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.