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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.