Expression and Proliferation-Promoting Role of Lymphoid Enhancer-Binding Factor 1 in Human Clear Cell Renal Carcinoma

Abstract

Lymphoid enhancer-binding factor 1 (LEF1) has been regarded as an important gene for carcinogenesis in many malignancies, however, the role of LEF1 in the progression of human renal cell carcinoma (RCC) has not been well studied. In this study, we investigated the expression of LEF1 in human RCC and the effect on proliferative ability of RCC cells. RCC samples from 138 patients who underwent radical nephrectomy were used in this study, the expression of LEF1 protein was determined by immunohistochemistry and Western blot, mRNA expression was analyzed by RT-PCR and real-time PCR. To investigate the effect of LEF1 on the proliferation of RCC cells, a LEF1 vector was transfected into RCC cells and LEF1 expression was also decreased by using siRNA. Proliferative ability of RCC cells was examined by WST-1 assay and a xenograft study with BALB/C nude mice. Our results indicated that LEF1 expression was significantly increased in stage III, IV and grade 3 RCC than in normal kidney, however, decreased LEF1 expression was found in low-stage and grade RCC compared to that in normal kidney, the expression of LEF1 was correlated to tumor stages, histologic grade, and tumor sizes in RCC. The effect of LEF1 on the proliferation in RCC was also analyzed, our results suggested that RCC cells expressing high levels of LEF1 had significantly increased proliferative ability compared to control cell lines, in contrast, RCC cells with a low LEF1 expression had lower proliferative ability. Moreover, LEF1 promoted proliferation of RCC cells depending on suppressing G2/M cell-cycle arrest. Our study demonstrated that the expression of LEF1 is associated with the progression of RCC and that LEF1 maybe involved in the development of RCC, these suggested LEF1 play a key role and might serve as a therapeutic target in treating advanced RCC.