USE OF TRANSCRIPTIONAL-ENHANCER ELEMENTS RESPONSIVE TO RAS, PROTEIN KINASE-A AND PROTEIN-KINASE-C TO EVALUATE INHIBITORS OF SPECIFIC SIGNAL-TRANSDUCTION PATHWAYS

To evaluate ras-mediated signal transduction, we constructed a transie nt transfection assay system that measures chloramphenicol acetyl tran sferase activity expressed under the transcriptional-enhancer elements responsive to ras, protein kinase C, and protein kinase A in NIH3T3 c ells. Characterization of the assay system with several known activato rs and inhibitors of signal transduction pathways proved that our syst em could reliably evaluate agents that affect individual pathways. Pir arubicin ((2''R)4'-tetrahydropyranyladriamycin, THP), which has recent ly been found able to reverse ras-transformed cells, appeared to selec tively inhibit the ras signal transduction pathway.