Gainer H S, Murray A W
Exp Cell Res. 1986 Sep;166(1):171-9. doi: 10.1016/0014-4827(86)90517-3.
The phorbol ester tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced several rapid changes in the HEL-37 mouse epidermal cell line. These included an alteration in cell morphology, inhibition of cell-cell communication, inhibition of epidermal growth factor (EGF) binding and a stimulation of phosphatidylcholine (PC) synthesis. The synthetic diacylglycerol sn 1-oleoyl-2-acetylglycerol (OAG) and sn 1,2-dioctanoylglycerol (diC8) caused similar changes, implying an involvement of the Ca2+- and phospholipid-dependent protein kinase (C-kinase). Treatment of the cells with the cAMP-generating agents db-cAMP and isoproterenol together with the phosphodiesterase inhibitors aminophylline and isobutyl-methylxanthine (IBMX) prior to and during TPA, OAG or diC8 treatment protected the cells against the inhibition of both junctional communication and EGF binding. TPA-induced morphological changes and enhanced PC synthesis, however, were unaffected by elevated levels of intracellular cAMP. These experiments provide evidence for the existence of a dual regulatory system controlling some (but not all) tumour promoter effects.
佛波酯肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）在HEL - 37小鼠表皮细胞系中诱导了几种快速变化。这些变化包括细胞形态的改变、细胞间通讯的抑制、表皮生长因子（EGF）结合的抑制以及磷脂酰胆碱（PC）合成的刺激。合成的二酰基甘油sn 1 - 油酰基 - 2 - 乙酰甘油（OAG）和sn 1,2 - 二辛酰甘油（diC8）引起了类似的变化，这意味着钙和磷脂依赖性蛋白激酶（C激酶）参与其中。在TPA、OAG或diC8处理之前和期间，用产生cAMP的试剂二丁酰环磷腺苷（db - cAMP）和异丙肾上腺素以及磷酸二酯酶抑制剂氨茶碱和异丁基甲基黄嘌呤（IBMX）处理细胞，可保护细胞免受连接通讯和EGF结合抑制的影响。然而，TPA诱导的形态变化和PC合成增强不受细胞内cAMP水平升高的影响。这些实验为存在控制某些（但不是全部）肿瘤促进剂效应的双重调节系统提供了证据。
