Issandou M, Darbon J M
INSERM U 168, Department of Endocrinology, CHU Rangueil Université Paul Sabatier, Toulouse, France.
Biochem Biophys Res Commun. 1988 Feb 29;151(1):458-65. doi: 10.1016/0006-291x(88)90615-8.
Exposure of MCF-7 human breast cancer cells to phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) results in a dose-dependent inhibition of cell proliferation. One of the earliest biochemical events induced by TPA is the translocation of protein kinase C from the cytosolic to the particulate compartment. We have investigated the effects of permeant diacylglycerol 1,2-dioctanoyl-glycerol (diC8) on both protein kinase C activity and MCF-7 cell proliferation. DiC8 induces a discrete but significant translocation of protein kinase C within the first minutes of MCF-7 cell treatment (26 +/- 6%, mean +/- SD of 5 different experiments, upon 5 min incubation in the presence of 43 micrograms/ml diC8). However, this effect is only transient as the enzymatic activity returns to the control value after 60 min. DiC8 mimics the effect of TPA on MCF-7 cell proliferation. The dose-response curves for both protein kinase C translocation and cell growth inhibition show that diC8 exerts its effects on both parameters in the same range of concentrations, despite some discrepancies at the lowest doses. We also report that long-term treatment of the cells with diC8 does not lead to the protein kinase C disappearance observed during prolonged exposure to TPA. All together, our results reinforce the hypothesis of a negative modulatory role of protein kinase C in MCF-7 cell proliferation and suggest that the enzyme translocation but not its down-regulation could be a pre-requisite in the biological cell response.
将MCF-7人乳腺癌细胞暴露于佛波酯，如12-O-十四酰佛波醇-13-乙酸酯（TPA），会导致细胞增殖受到剂量依赖性抑制。TPA诱导的最早生化事件之一是蛋白激酶C从胞质溶胶向颗粒区室的转位。我们研究了渗透性二酰甘油1,2-二辛酰甘油（diC8）对蛋白激酶C活性和MCF-7细胞增殖的影响。在MCF-7细胞处理的最初几分钟内，diC8诱导蛋白激酶C发生离散但显著的转位（在43微克/毫升diC8存在下孵育5分钟后，5次不同实验的平均值±标准差为26±6%）。然而，这种效应只是短暂的，因为酶活性在60分钟后恢复到对照值。diC8模拟了TPA对MCF-7细胞增殖的作用。蛋白激酶C转位和细胞生长抑制的剂量反应曲线表明，diC8在相同浓度范围内对这两个参数都有作用，尽管在最低剂量时有一些差异。我们还报告说，用diC8对细胞进行长期处理不会导致在长期暴露于TPA期间观察到的蛋白激酶C消失。总之，我们的结果强化了蛋白激酶C在MCF-7细胞增殖中起负调节作用的假设，并表明酶的转位而非其下调可能是生物细胞反应的先决条件。
