Leavitt J, Gunning P, Kedes L, Jariwalla R
Nature. 1985;316(6031):840-2. doi: 10.1038/316840a0.
Heteroploid mouse NIH 3T3 fibroblasts and several rat fibroblast strains (Rat-1, Rat-2 and REF-52) are cell lines of special interest in the field of carcinogenesis because of their extensive use as normal cells in transformation assays for putative cancer-causing genes. Exposure of these cells to carcinogenic chemicals or oncogenic DNA produces anchorage-independent cells with retracted cytoplasms that lack actin cables. All human fibroblast strains, normal and transformed, synthesize two electrophoretic forms of actin (beta- and gamma-actin). In contrast, we discovered that early-passage mouse and rat strains synthesize abundant amounts of each of the three electrophoretic forms of actin (alpha-, beta- and gamma-actin) but mouse and rat cancer cells express only beta- and gamma-actins. We now show that in NIH 3T3 and Rat-2 fibroblasts a third actin, the smooth muscle alpha isoform, is abundantly co-expressed with beta- and gamma-actin. In every instance tested following transformation to tumorigenicity, the accumulation of alpha-actin messenger RNA and alpha-actin synthesis was greatly inhibited. Shutdown of alpha-actin expression thus appears to be a reproducible transformation-sensitive marker in rodent fibroblasts.
异倍体小鼠NIH 3T3成纤维细胞和几种大鼠成纤维细胞系（Rat-1、Rat-2和REF-52）在致癌作用领域具有特殊意义，因为它们在假定致癌基因的转化试验中被广泛用作正常细胞。将这些细胞暴露于致癌化学物质或致癌DNA会产生具有收缩细胞质且缺乏肌动蛋白丝束的不依赖贴壁的细胞。所有正常和转化的人成纤维细胞系都能合成两种电泳形式的肌动蛋白（β-肌动蛋白和γ-肌动蛋白）。相比之下，我们发现早期传代的小鼠和大鼠细胞系能合成大量三种电泳形式的肌动蛋白（α-肌动蛋白、β-肌动蛋白和γ-肌动蛋白），但小鼠和大鼠癌细胞仅表达β-肌动蛋白和γ-肌动蛋白。我们现在表明，在NIH 3T3和Rat-2成纤维细胞中，第三种肌动蛋白，即平滑肌α异构体，与β-肌动蛋白和γ-肌动蛋白大量共表达。在每一个经测试的致瘤性转化实例中，α-肌动蛋白信使核糖核酸的积累和α-肌动蛋白的合成均受到极大抑制。因此，α-肌动蛋白表达的关闭似乎是啮齿动物成纤维细胞中一种可重复的转化敏感标志物。
