Differential c-jun expression in response to tumor promoters in JB6 cells sensitive or resistant to neoplastic transformation.
The activity of AP-1, a trans-acting transcription factor, is stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. TPA and EGF also promote neoplastic transformation only in P+ cells. Thus, it has been proposed that AP-1-dependent gene expression is involved in determining sensitivity to tumor promotion. This paper explores the possible basis for the differential inducibility of AP-1 activity in P+ and P- JB6 cells, focusing in particular on the regulation of expression of the components of the AP-1 complex at the mRNA level. The expression of jun and fos gene family members, which make up the AP-1 complex, can be stimulated by serum and a number of growth factors, including EGF, and by TPA. Therefore, the possibility that differential expression of one or more forms of jun or fos contributes to the differential AP-1 activity was considered. The data presented here demonstrate both similarities and differences in the basal and TPA- or EGF-induced levels of fos and jun family members between P+ and P- cells. The most striking observation was that the overall TPA- and EGF-induced levels of jun but not fos expression were higher in P+ cells. This suggests that tumor promoter-regulated c-jun expression may contribute to the differential AP-1 activation observed in these cells and may be important in determining sensitivity to promotion of neoplastic transformation.
Ben-Ari
E T
ET
Cell Biology Section, National Cancer Institute, Frederick, MD 21702-1201.
Bernstein
L R
LR
Colburn
N H
NH
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D066298:In Vitro Techniques; D051379:Mice; D009368:Neoplasm Transplantation; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D013755:Tetradecanoylphorbol Acetate