Complex Regulation of a Tumor Marker Expression. Enhancer and Silencer of the GST-P Gene

Abstract

MURAMATSU, M., DICCIANNI, M.B., MORIMURA, S., SUZUKI, T. and IMAGAWA, M. Complex Regulation of a Tumor Marker Expression. Enhancer and Silencer of the GST-P Gene. Tohoku J. Exp. Med., 1992, 168 (2), 175-182-Glutathione transferase P (GST-P) is expressed at high levels in precancerous lesions and hepatocellular carcinomas from a very early stage of chemically-induced hepatocarcinogenesis in the rat. To explore the molecular mechanisms of its specific activation, we are investigating the regulation mechanisms of the GST-P gene expression. By using gene technology, we have identified a strong enhancer, GPEI, at 2.5Kb and a silencer region at about 400 by upstream from the transcription start site. GPEI has a palindromic structure composed of two TPA- responsive element (TRE)-like sequences and binds at least three proteins including AP-1 (c-jun/c-fos). The silencer is composed of several sequences resembling each other and binds at least three proteins including SF-B/LAP/LIP. To determine whether the GST-P gene is activated together with a putative hepato- oncogene because they are located close to each other (cis-mechanism), or because they share a trans-acting factor that can activate both genes simultaneously (trans-mechanism), transgenic rats were produced with GST-P control region connected to the CAT reporter. The results unequivocally demonstrate that GST-P gene is activated position-independently by a trans-mechanism. -AP-1; enhancer; hepatocarcinogenesis; glutathione transferase P gene; silencer