Kakunaga T
Gan To Kagaku Ryoho. 1984 Mar;11(3 Pt 2):629-37.
Alteration of cell shape, motility and membrane fluidity which result in the disorganized cell arrangement and orientation, uncontrolled cell growth, and abnormal response to the environment have been considered one of the most striking and universal phenotypes characteristics of neoplastic cells. Cytoplasmic actins, i.e., beta-and gamma-actin, are the major molecules of the cytoskeleton whose function is involved in maintaining and controlling cell morphology, motility and membrane fluidity. In fact, most transformed cells show abnormal and disorganized structure of actin cable network. Thus, it is conceivable that alteration of structure and function of actin or microfilament may lead the cells to express the transformed phenotypes. A new polypeptide recognized in a chemically transformed human fibroblast line was identified as a variant form of actin. mRNA coding for the variant actin was detected only in this particular transformed line. The size and cross-hybridizability with dictyostelium actin cDNA of mRNA coding for the variant actin and complete amino acid sequence of the variant actin indicate that the new variant actin is a mutated beta-actin. Only a single amino acid (glycine) at the position of 245 was substituted by aspartic acid. This substitution corresponds to a GC----AT transition, a point mutation. On the other hand, the highly malignant cell variant was isolated from the transformed line. The mutated beta-actin was further altered in this highly malignant subclone. This further altered mutant beta-actin showed more negative charge, rapid synthetic ratio, and short halflife in the cells. The incorporation of the mutated beta-actin into cytoskeleton was significantly reduced. A hypothesis on the role of alteration of actin and microfilament in oncogenic transformation is proposed.
细胞形状、运动性和膜流动性的改变导致细胞排列和定向紊乱、细胞生长失控以及对环境的异常反应，这些被认为是肿瘤细胞最显著和普遍的表型特征之一。细胞质肌动蛋白，即β-肌动蛋白和γ-肌动蛋白，是细胞骨架的主要分子，其功能涉及维持和控制细胞形态、运动性和膜流动性。事实上，大多数转化细胞显示出肌动蛋白丝网络的异常和紊乱结构。因此，可以想象，肌动蛋白或微丝的结构和功能改变可能导致细胞表达转化表型。在化学转化的人成纤维细胞系中识别出的一种新多肽被鉴定为肌动蛋白的变体形式。编码该变体肌动蛋白的mRNA仅在这个特定的转化系中被检测到。编码该变体肌动蛋白的mRNA的大小、与盘基网柄菌肌动蛋白cDNA的交叉杂交性以及该变体肌动蛋白的完整氨基酸序列表明，新的变体肌动蛋白是一种突变的β-肌动蛋白。仅在245位的单个氨基酸（甘氨酸）被天冬氨酸取代。这种取代对应于一个GC→AT的转换，即一个点突变。另一方面，从转化系中分离出高度恶性的细胞变体。在这个高度恶性的亚克隆中，突变的β-肌动蛋白进一步发生了改变。这种进一步改变的突变型β-肌动蛋白在细胞中显示出更多的负电荷、更快的合成速率和更短的半衰期。突变的β-肌动蛋白掺入细胞骨架的量显著减少。提出了一个关于肌动蛋白和微丝改变在致癌转化中的作用的假说。
