有丝分裂诱导基因6(MIG-6)可诱导人成纤维细胞发生提前衰老

Mitogen-inducible Gene 6 (MIG-6) Induces Normal Human Fibroblast Cell Premature

年老细胞许多基因表达发生变化,其中有些基因的表达可以诱导成纤维细胞早衰.癌基因诱导的衰老(oncogene-induced senescence,OIS)是由一些连续癌症基因的信号,以阻止细胞增殖造成的反应.有丝分裂诱导基因6(mitogen-inducible gene-6,MIG-6)是一个抑癌基因,是ErbB RTK通路的负调控因子,抑制肿瘤细胞增殖.本文以人胚肺二倍体成纤维细胞为对象,研究MIG-6蛋白在细胞衰老中的作用.通过Western印迹发现,在老年细胞中MIG-6表达升高.利用逆转录病毒载体将MIG-6基因转入年轻的人胚肺二倍体成纤维细胞中,通过Western印迹方法检测是否过表达MIG-6,然后通过SA-β-gal染色检测其阳性率,发现转染MIG-6基因后的成纤维细胞SA-β-gal染色率明显高于对照组,生长缓慢.实验结果证实,MIG-6蛋白可以诱导人二倍体成纤维细胞提前衰老.

In senescent cells,gene expression is different from that in young cells and some of them can induce human fibroblast cell premature.Oncogene-induced senescence （OIS） is a robust and sustained anti-proliferative response brought about by oncogenic signaling.Evidence shows that mitogen-inducible gene 6 （MIG-6） is a tumor suppressor gene.MIG-6 acts as a negative feedback regulator of the ErbB RTK pathway,and inhibits tumor cell proliferation.In this article we used human embryonic lung diploid fibroblast cell as a model to study the role of MIG-6 in the progress of cell senescence.Through Western blotting we found that the expression of MIG-6 in senescent cells increased.We constructed retroviral MIG-6 cDNA vector and transfected it into normal human fibroblast cells and analyzed MIG-6 expression in transfected cells.Then we examined the β-gal activity of HDF cells transfected with MIG-6 cDNA and found that the ratio of stained cells in transfected cells was much more than control cells,and the growth rate decreased.It was concluded that the over-expression of MIG-6 protein induced human embryonic lung diploid fibroblast cell premature.