cis- and trans-Acting Genetic Elements Responsible for Induction of Specific Genes by Tumor Promoters, Serum Factors, and Stress

This chapter discusses the genetic mechanisms that underlie the ultraviolet response. During the early characterization of the UV response in cultured human fibroblasts, it became apparent that treatment of these cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) leads to induction of most of the same peptides induced by UV or mitomycin C. Treatment of cultured mammalian cells with phorbol ester tumor promoters such as TPA causes a variety of pleiotropic effects, most of which are probably mediated by the activation of protein kinase C, the major cellular target for these agents. Many of the genes are also induced after treatment of cells with agents such as phorbol esters, serum growth factors, and lymphokines, which in most cases do not lead to direct deoxyribonucleic acid damage. However, based on genetic analysis, it appears that common cis- and trans-acting elements participate in mediating the transcriptional response to these agents.