Complex regulation of a tumor marker expression. Enhancer and silencer of the GST-P gene.
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 2.5 Kb and a silencer region at about 400 bp 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.
Muramatsu
M
M
Department of Biochemistry, Saitama Medical School, Japan.
Diccianni
B
B
Morimura
S
S
Suzuki
T
T
Imagawa
M
M
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D004926:Escherichia coli / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016678:Genome; D005982:Glutathione Transferase; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D051381:Rats
D014408:Biomarkers, Tumor; D015500:Chloramphenicol O-Acetyltransferase; D005982:Glutathione Transferase