The tumor promoter pristane activates transcription by a cAMP dependent mechanism

Abstract

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.