Constitutive synthesis of activator protein 1 transcription factor after viral transformation of mouse fibroblasts

Abstract

Transcription factor activator protein 1 (AP1) interacts with the promoter region of a number of genes that are stimulated by growth factors present in serum or by agents such as phorbol 12-myristate 13-acetate (PMA) that partially mimic their action. To investigate the possible role of AP1 in the control of cellular growth and in transformation of mammalian cells, we monitored its activity by binding to a specific DNA probe in normal or transformed mouse NIH 3T3 cells. A 3- to 4-fold increase in the DNA-binding activity was found after serum stimulation of quiescent NIH 3T3 cells. A 2- to 3-fold activation was found after treatment with PMA or dibutyryl-cAMP, suggesting that different signal-transducing pathways could activate AP1 factor in these cells. PMA stimulation was dependent on new protein synthesis. In contrast to normal cells, a high serum-independent AP1 DNA-binding activity was found in NIH 3T3 cells transformed by simian virus 40. These results suggest that constitutive AP1 synthesis may be a crucial step in cellular transformation.