Gene Regulation and Genetic Susceptibility to Neoplastic Transformation: AP-1 and p80 Expression in JB6 Cells

• Published in: Environmental health perspectives 1991-06, Vol.93, p.111-119
• Main Authors: Bernstein, Lori R., Ben-Ari, Elia T., Simek, Stephanie L., Colburn, Nancy H.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Carcinogenesis; Carcinogens; Carcinogens - pharmacology; Cell Line, Transformed; Cell lines; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; Cells; Clone Cells - drug effects; Clone Cells - pathology; Cooperativity between Genes; Enhancer Elements, Genetic; Epidermal cells; Epidermis - cytology; Gene Expression Regulation, Neoplastic - drug effects; Genes; Genetic Predisposition to Disease; Messenger RNA; Mice; Mice, Inbred BALB C - genetics; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphorylation; Protein Binding - drug effects; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Fusion Proteins - biosynthesis; RNA; RNA, Messenger - biosynthesis; RNA, Neoplasm - biosynthesis; Transactivation; Transcriptional Activation - drug effects; Tumors
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.9193111

The mouse epidermal JB6 cell system consists of clonal genetic variants that are sensitive ( P+) or resistant ( P-) to the promotion of neoplastic transformation by phorbol esters and other tumor-promoting agents. P+cells display AP-1-dependent phorbol-ester-inducible transactivation of gene expression, whereas P-cells have a defect in transactivation. Transfection of promotion sensitivity gene pro-1 into P-cells reconstituted both P+phenotype and AP-1-dependent phorbol-ester-inducible transactivation. P-and P+cells exhibited induction of c-jun and c-fos messenger RNA levels by phorbol ester, but P-cells had significantly lower basal and induced levels of jun mRNA than P+cells. Basal and induced levels of c-jun protein were significantly lower in P-cells as well. Differences in levels the 80-kDa pI 4.5 protein p80 were also observed in JB6 cells as a function of preneoplastic progression; high levels of p80 protein and mRNA were observed in P-cells, intermediate levels in P+cells, and negligible levels were observed in transformed derivatives of JB6 cells. Phorbol ester treatment induced phosphorylation but not synthesis of p80. These data are consistent with the hypotheses that AP-1 is required in the signal transduction pathway for promotion of neoplastic transformation by tumor promoter, that pro genes may control AP-1 activity, that threshold levels of Jun mRNA and protein may play a role in transactivation and promotion sensitivity, and that the p80 protein in JB6 cells may behave in vivo as a suppressor of cellular transformation.