Science · 1989 · 208 citations · 28 references
MedicineGeneticsMolecular BiologyGene ExpressionSignal TransductionTranscriptional RegulationNeoplastic TransformationOncogene ActivationOncogenic Signaling PathwaysProto-oncogene ActivationSignal Transduction In CancerTumor PromotionChloramphenicol AcetyltransferaseMolecular Mechanisms Of CarcinogenesisNeoplastic DiseaseNeoplastic ProgressionOncogene RegulationReporter Gene ConstructionReporter Gene SystemsTumor Promoter Mechanisms
Tumor promoters may bring about events that lead to neoplastic transformation by inducing specific promotion-relevant effector genes. Functional activation of the transacting transcription factor AP-1 by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) may play an essential role in this process. Clonal genetic variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to promotion of transformation by TPA were transfected with 3XTRE-CAT, a construct that has AP-1 cis-enhancer sequences attached to a reporter gene encoding chloramphenicol acetyltransferase (CAT). Transfected JB6 P+, but not P- variants, showed TPA-inducible CAT synthesis. Epidermal growth factor, another transformation promoter in JB6 cells, also caused P+ specific induction of CAT gene expression. These results demonstrate an association between induced AP-1 function and sensitivity to promotion of neoplastic transformation.
28