Isakov N, Bleackley R C, Shaw J, Altman A
Biochem Biophys Res Commun. 1985 Jul 31;130(2):724-31. doi: 10.1016/0006-291x(85)90476-0.
The tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) affects a wide variety of cellular functions via its binding to protein kinase C (PKC). The TPA molecule contains a diacylglycerol (DAG)-like structure, which may explain its ability to mimic DAG in PKC activation. Teleocidin (TCD) is a different tumor promoter which can compete with TPA in binding to its cell surface receptors even though structurally unrelated to TPA or DAG. Since TCD may use an additional receptor system and/or be distinguished from TPA in its effect on cells, we compared the effects of TPA and TCD on human peripheral blood lymphocytes (PBL). Both tumor promoters preferentially enhanced cell proliferation of sheep erythrocyte-rosetted lymphocytes, which were enriched for T cells. Additionally, TPA and TCD both induced a high density of cell surface receptors for interleukin 2 (IL2) and transferrin, but not synthesis or production of IL2. However, either of the tumor promoters synergized with T cell mitogens to induce high level IL2 production by PBL. In dose response and kinetic studies, matching concentrations of TPA and TCD induced similar effects in PBL. The results thus demonstrate that TPA and TCD are alike in mitogenic capacity, and suggest that structural similarity between the tumor promoter and DAG, the physiological activator of PKC, is not an essential property for promoting tumors or affecting a wide variety of cellular functions.
肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯(TPA)通过与蛋白激酶C(PKC)结合影响多种细胞功能。TPA分子含有类似二酰基甘油(DAG)的结构,这可能解释了它在激活PKC时模拟DAG的能力。杀鱼菌素(TCD)是一种不同的肿瘤促进剂,尽管其结构与TPA或DAG无关,但它能在与细胞表面受体结合方面与TPA竞争。由于TCD可能使用额外的受体系统和/或在对细胞的作用上与TPA不同,我们比较了TPA和TCD对人外周血淋巴细胞(PBL)的影响。两种肿瘤促进剂都优先增强了富含T细胞的绵羊红细胞玫瑰花结形成淋巴细胞的细胞增殖。此外,TPA和TCD都诱导了白细胞介素2(IL2)和转铁蛋白的高密度细胞表面受体,但不诱导IL2的合成或产生。然而,任何一种肿瘤促进剂都能与T细胞有丝分裂原协同作用,诱导PBL产生高水平的IL2。在剂量反应和动力学研究中,匹配浓度的TPA和TCD在PBL中诱导了相似的效应。因此,结果表明TPA和TCD在促有丝分裂能力方面相似,并表明肿瘤促进剂与PKC的生理激活剂DAG之间的结构相似性,对于促进肿瘤或影响多种细胞功能并非必需特性。