整合素αvβ6调控结肠癌细胞转录因子Ets-1表达的分子机制研究

Signaling and regulatory mechanisms of integrin αvβ6 on the expression of Ets-1 of colon cancer cells

目的:探讨整合素αvβ6对核转录因子Ets-1表达的影响,明确αvβ6-ERK2直接连接在该过程中发挥的作用。方法:流式细胞仪检测各结肠癌SW480细胞表面αvβ6的表达;采用Westernblotting法分别检测ERK表达、活化水平和Ets-1的表达水平。结果:SW480β6和SW480β6Del.mutant细胞均表达αvβ6;SW480β6细胞Ets-1的表达量较SW480细胞明显增多(P<0.05),同时ERK的磷酸化水平(p-ERK)也明显升高,而总ERK(t-ERK)表达水平二者无明显差异;SW480β6Del.mutant细胞ERK2的磷酸化水平较SW480β6细胞明显降低;SW480β6Del.mutant细胞和PD98059处理的SW480β6细胞Ets-1的表达水平明显低于对照组(P<0.05)。结论:整合素αvβ6通过αvβ6-ERK2直接连接提高ERK2的磷酸化水平,从而促进结肠癌SW480细胞核转录因子Ets-1表达。

Objective： To explore the effects of the integrin αvβ6 on the expression of nuclear transcription factor Ets-1,and to determine the role of αvβ6-ERK2 direct binding in this process.Methods： FACScan analyses were applied to detect the αvβ6 expression in colon cancer cell SW480 groups.The expression and activation level of ERK,as well as the expression level of Ets-1 were detected by western blotting.Results： Both SW480β6 and SW480β6Del.mutant cells were expressing αvβ6.The amount of Ets-1 expression in SW480β6 cells was higher than that in SW480 cells.Compared with SW480β6 cells,the level of phosphorylated ERK（p-ERK）decreased in SW480 cells,with no significant change on total ERK（t-ERK） expression.The SW480β6Del.mutant cells lacking the ERK2 binding sites reduce the amount of phosphorylated ERK2.Both PD98059 treated SW480β6 cells and SW480β6Del.mutant cells had a lower level of Ets-1 expression than control groups.Conclusion： Integrin αvβ6 promotes the phosphorylation of ERK2 through αvβ6-ERK2 direct binding,thereby facilitating the Ets-1 expression.