Lee S H, Ackland-Berglund C E, Jones C J
Dept. of Veterinary Science, University of Nebraska, Lincoln 68583-0905.
Mol Cell Biochem. 1992 Mar 4;110(1):75-81. doi: 10.1007/BF02385008.
Pristane is a naturally occurring isoprenoid which is believed to be derived from the phytyl moiety of chlorophyll. Thus it is not surprising that pristane is present in many common fruits or vegetables and furthermore can be detected in tissues of fish and mammals. Using the rat as an animal model, pristane can function as a potent tumor promoter. It is conceivable that pristane could play a role in the development of certain malignancies in higher mammals since it is commonly found in the diet. At the molecular level, pristane can induce changes in the plasma membrane, alter the conformation of chromatin, as well as selectively activate gene expression. This study was undertaken to identify specific transcriptional motifs which are responsive to pristane. A transcriptional promoter which contained a cAMP response element (CRE) was consistently stimulated by pristane in several mouse and primate cell lines. A promoter construct which contained a single copy of the TPA response element (TRE) was also activated by pristane but surprisingly a promoter which contained multiple copies of the TRE was not. Activation of the TRE required 10 fold higher concentrations of pristane relative to activation of the CRE. Within two hours after addition of pristane to monkey fibroblasts (CV-1) levels of cAMP were increased more than two fold relative to controls. These data indicated that pristane can increase the level of cAMP in CV-1 cells and consequently stimulate transcriptional promoters which contain a CRE.
降植烷是一种天然存在的类异戊二烯，据信它源自叶绿素的植基部分。因此，降植烷存在于许多常见水果或蔬菜中，并且还能在鱼类和哺乳动物的组织中被检测到，这并不奇怪。以大鼠作为动物模型，降植烷可作为一种强效的肿瘤促进剂。鉴于降植烷在饮食中普遍存在，可以想象它可能在高等哺乳动物某些恶性肿瘤的发生发展中起作用。在分子水平上，降植烷可诱导质膜发生变化、改变染色质构象以及选择性地激活基因表达。本研究旨在鉴定对降植烷有反应的特定转录基序。在几种小鼠和灵长类细胞系中，含有环磷酸腺苷反应元件（CRE）的转录启动子始终受到降植烷的刺激。含有单个佛波酯反应元件（TRE）拷贝的启动子构建体也被降植烷激活，但令人惊讶的是，含有多个TRE拷贝的启动子却未被激活。相对于CRE的激活，TRE的激活需要高10倍浓度的降植烷。在向猴成纤维细胞（CV - 1）中添加降植烷后两小时内，环磷酸腺苷水平相对于对照增加了两倍多。这些数据表明，降植烷可提高CV - 1细胞中环磷酸腺苷的水平，从而刺激含有CRE的转录启动子。
