Alexandrova A, Ivanov A, Chumakov P, Kopnin B, Vasiliev J
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Oncogene. 2000 Nov 23;19(50):5826-30. doi: 10.1038/sj.onc.1203944.
Effects of p53 expression on cell morphology and motility were studied using the derivatives of p53-null 10(1) mouse fibroblasts with tetracycline-regulated expression of exogenous human p53. Induction of p53 expression was accompanied by significant decrease in extracellular matrix (fibronectin) and reduction of matrix fibrils, diminution of the number and size of focal contacts, decrease of cell areas, establishment of more elongated cell shape and alterations of actin cytoskeleton (actin bundles became thinner, their number and size decreased). Expression of His175 and Gln22/ Ser23 p53 mutants caused no such effects. To study the influence of p53 expression on cell motility we used wound technique and videomicroscopy observation of single living cells. It was found that induction of p53 expression led to increase of lamellar activity of cell edge. However, in spite of enhanced lamellar activity p53-expressing cells migrated to shorter distance and filled the narrow wound in longer time as compared with their p53-null counterparts. Possible mechanisms of the influence of p53 expression on cell morphology and motility are discussed.
利用四环素调控外源人p53表达的p53基因敲除10(1)小鼠成纤维细胞衍生物,研究了p53表达对细胞形态和运动性的影响。p53表达的诱导伴随着细胞外基质(纤连蛋白)的显著减少和基质纤维的减少,粘着斑数量和大小的减小,细胞面积的减小,更细长细胞形状的形成以及肌动蛋白细胞骨架的改变(肌动蛋白束变细,其数量和大小减少)。His175和Gln22/Ser23 p53突变体的表达未产生此类影响。为了研究p53表达对细胞运动性的影响,我们采用了伤口技术并对单个活细胞进行视频显微镜观察。发现p53表达的诱导导致细胞边缘片状活动增加。然而,尽管片状活动增强,但与p53基因敲除的对应细胞相比,表达p53的细胞迁移距离较短,填充狭窄伤口的时间较长。讨论了p53表达影响细胞形态和运动性的可能机制。