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通过改变细胞骨架诱导永生化人支气管上皮细胞的锚定非依赖性生长和血清抗性。

Induction of anchorage independent growth and serum resistance in immortalized human bronchial epithelial cells by alteration of the cytoskeleton.

作者信息

De Silva R, Englezou A, Schevzov G, Gerwin B I, Harris C C, Gunning P, Reddel R R

机构信息

Cancer Research Unit, Children's Medical Research Institute, Westmead, Sydney, N.S.W., Australia.

出版信息

Cell Mol Biol Res. 1994;40(4):323-35.

PMID:7866433
Abstract

Malignant transformation is frequently accompanied by obvious changes in cytoarchitecture, but the importance of these changes has been difficult to assess in view of the large number of other cellular changes that also occur. In this study, we transfected the SV40-immortalized human bronchial epithelial cell line, BEAS-2B, with human wild-type beta or gamma actin gene expression plasmids to induce cytoskeletal changes and to determine whether this was associated with altered cellular growth properties. Cells expressing the exogenous full-length actin genes underwent a fibroblastoid change in morphology which was reflected in changes in their pattern of actin cable organization, and acquired both the ability to grow under anchorage-independent conditions and resistance to the normal growth inhibitory effects of fetal bovine serum. These phenotypic changes correlated with changes in actin mRNA levels, but not with changes in actin protein levels. The phenotypically altered cells were not tumorigenic when injected subcutaneously in athymic nude mice, and they retained the ability to suppress the tumorigenic potential of a lung carcinoma cell line, HuT-292. Therefore, alteration of the cytoskeleton of immortalized human bronchial epithelial cells resulted in the acquisition of some properties commonly found in malignant cells, but did not result in tumorigenicity.

摘要

恶性转化常常伴随着细胞结构的明显变化,但鉴于同时发生的大量其他细胞变化,这些变化的重要性一直难以评估。在本研究中,我们用人类野生型β或γ肌动蛋白基因表达质粒转染了SV40永生化的人支气管上皮细胞系BEAS - 2B,以诱导细胞骨架变化,并确定这是否与细胞生长特性的改变有关。表达外源性全长肌动蛋白基因的细胞在形态上发生了成纤维样改变,这反映在其肌动蛋白丝组织模式的变化上,并且获得了在非贴壁条件下生长的能力以及对胎牛血清正常生长抑制作用的抗性。这些表型变化与肌动蛋白mRNA水平的变化相关,但与肌动蛋白蛋白水平的变化无关。当在无胸腺裸鼠皮下注射时,表型改变的细胞不具有致瘤性,并且它们保留了抑制肺癌细胞系HuT - 292致瘤潜能的能力。因此,永生化人支气管上皮细胞的细胞骨架改变导致获得了一些恶性细胞中常见的特性,但并未导致致瘤性。

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