Glioma cell proliferation mechanism regarding the signal transduction system in vivo.

1. 近年来，细胞生物学的主要进展是阐明了与细胞表面受体相关的一系列细胞内信号通路。研究最广泛的信号通路之一是磷脂酶C依赖的膜磷酸肌醇水解形成肌醇多磷酸和二酰基甘油。我们研究了肿瘤增殖的信号转导机制，发现中枢神经系统和胶质瘤之间磷脂转换的代谢差异。采用体内放射自显影技术观察了碳-11标记的1,2 -二酰基甘油（DAG）在大鼠脑和移植的大鼠胶质瘤（C_6胶质瘤）中的摄取情况。移植细胞中显示明显的DAG摄取，表明胶质瘤中的磷脂转换比中枢神经系统更促进。胶质瘤细胞的代谢部分也存在差异，细胞同时产生放射性磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE），同时产生磷脂酸（PA）、磷脂酰肌醇（PI）和磷脂肌醇（PIP和PIP_2）。这提示了以PI-PKC（蛋白激酶C）系统解离为代表的肿瘤信号转导系统的特殊性2。在我们使用生长因子的研究中，我们发现在每次刺激中，肿瘤信号转导都有许多反应。PDGF与EGF的反应有明显差异。血小板衍生生长因子主要激活PC-PLD（磷脂酶D）系统，提示PI-PKC解离，类似于TPA。我们认为肿瘤信号转导应受“双磷脂转换系统”的调控，即PI-PCL和PC-PLD，处于较高的信号层次。

1. The major advance in cell biology in recent has been the clarification of a series of intracellular signaling pathways that link to the cell surface receptors. One of the most extensively studied signaling pathways is the phospholipase C dependent hydrolysis of membrane phosphoinositides to form inositol polyphosphate and diacylglycerols. We studied the tumor signal transduction mechanism regarding tumor proliferation and we found the metabolic difference in phospholipid turnover between the CNS and the glioma. Carbon-11-labeled 1, 2-diacylglycerol(DAG) uptake was observed in rat brain and transplanted rat glioma (C_6 glioma) using in vivo autoradiographic technique. Marked DAG uptake was shown in the transplanted cells, suggesting that phospholipid turnover in the glioma was prompted than the CNS. Chromatographic studies also showed the difference in the metabolic fraction, in which glioma cells simultaneously produced radioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accompanied with phosphatidic acids (PA), phosphatidylinositols(PI) and phosphoinositides(PIP and PIP_2). This suggest specific feature of the tumor signal transduction system represented by the dissociation of PI-PKC (protein kinase C) system.2. In our studies with using growth factors, we found the fact that the many responses were observed in the tumor signal transduction in each stimulation. There was obvious difference in the response between PDGF and EGF. Platelet derived growth factor predominantly activated PC-PLD(phospholipase D) system, suggesting the PI-PKC dissociation, based on analogy to TPA. We conclude that the tumor signal transduction should be regulated by "dual phospholipid turnover system", i. e. PI-PCL and PC-PLD, positioned in te higher signaling hierarchy.