蛋白磷酸酶4在人肺癌细胞A549增殖中的功能分析

蛋白磷酸酶4(PP4)是PP2A亚家族的重要成员之一.已有研究表明PP4在果蝇与线虫中参与了中心体成熟,但作为一个进化上高度保守的蛋白质,PP4在哺乳动物细胞中的确切功能至今仍知之甚少.选择人肺癌细胞A549为材料,转染发夹型siRNA表达质粒,筛选鉴定获得了PP4表达抑制细胞株,然后对细胞的形态、生长特性及有丝分裂过程进行观察分析.与对照细胞相比,发现其生长速率明显减慢,细胞群体中DNA含量为4N的细胞比率明显增高.这一结果是由细胞群体中出现了高比例的多核细胞造成的,进一步的分析揭示,高比例多核细胞的产生是由于PP4表达下降,致使细胞有丝分裂和胞质分裂受到严重干扰所导致的.由此推测PP4对于保证细胞有丝分裂及胞质分裂的正常进行具有重要作用,PP4受到抑制将会导致多核细胞的产生,进而抑制A549细胞的增殖.

Function Analysis of PP4 on Proliferation of A549 Human Lung Adenocarcinoma Cells

Protein phosphatase 4(PP4)is an important protein serine/threonine phosphatase belonging to PP2A family.Previous study showed that protein phosphatase 4 played an important role in centrosome maturation in D.melanogaster and C.elegans.But as an evoulutional conserved phosphatase,little was known on its function in mammalian cells.siRNA expression vector was used to suppress PP4 expression in A549 and clonal cell lines was obtained in which the expression of PP4 was inhibited.The morphology,growth and mitosis process of the cells were investigated.It was found that cell growth and proliferation were greatly inhibited and many cells became multinuclei comparing with the control cells.Further study showed that the mitosis and cytokinesis became abnormal in PP4 silencing cells.It was proposed that PP4 played an important role in mitosis and cytokinesis.PP4 expression suppression resulted in multinucleus,then inhibited the proliferation of cells.