Rifkin D B, Crowe R M, Pollack R
Cell. 1979 Oct;18(2):361-8. doi: 10.1016/0092-8674(79)90055-2.
We have examined the effect of the tumor promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), on the actin-containing elements of the cytoskeleton of chick embryo fibroblasts (CEF). TPA at concentrations as low as 7.3 times 10-10M indices a reversible change in the cytoskeleton as visualized by indirect immunofluorescence using anti-actin antibodies. Cells incubated with TPA lose the ordered actin-containing structures found in normal cells and resemble Rous sarcoma virus-transformed cells in that the immunofluorescent actin pattern is diffuse. The TPA effects are both dose-and time-dependent. Analogs of TPA which are inactive as tumor promoters do not induce cytoskeletal changes at the concentrations tested, while a second tumor promoter, PDD, is also able to cause alterations in actin-containing structures. The action of TPA requires de novo synthesis of both RNA and protein. The direct cytoskeletal changes are neither plasmin-dependent nor subject to inhibition by incubating the cells with high levels of protease inhibitors during the exposure to TPA. However, plasminogen does increase the sensitivity of cells to TPA.
我们研究了肿瘤启动子12-0-十四烷酰佛波醇-13-乙酸酯（TPA）对鸡胚成纤维细胞（CEF）细胞骨架中含肌动蛋白成分的影响。低至7.3×10⁻¹⁰M浓度的TPA会使细胞骨架发生可逆变化，这通过使用抗肌动蛋白抗体的间接免疫荧光观察到。用TPA孵育的细胞失去了正常细胞中有序的含肌动蛋白结构，并且在免疫荧光肌动蛋白模式呈弥漫状这一点上类似于劳氏肉瘤病毒转化的细胞。TPA的作用具有剂量和时间依赖性。作为肿瘤启动子无活性的TPA类似物在测试浓度下不会诱导细胞骨架变化，而另一种肿瘤启动子PDD也能够引起含肌动蛋白结构的改变。TPA的作用需要RNA和蛋白质的从头合成。直接的细胞骨架变化既不依赖纤溶酶，在暴露于TPA期间用高水平蛋白酶抑制剂孵育细胞也不会对其产生抑制作用。然而，纤溶酶原确实会增加细胞对TPA的敏感性。
