The JB6 cell system of mouse epidermal cells consists of a battery of clonal genetic variants in various stages of progression toward a neoplastic endpoint. These cells provide a model system for evaluating rate limiting and essential components in the signal transduction apparatus for neoplastic transformation induced by tumor promoting agents. Previously, we reported that calls which are sensitive to promotion of transformation by tumor promoters (called P+ cells) have tumor promoter inducible AP-1 transcriptional activity, whereas cells resistant to promotion of transformation by tumor promoters (called P- cells) do not. c-Jun protein expression and P-1 activity are required for P+ phenotypic responsiveness to tumor promoters since dominant negative c-Jun mutants block cJun expression, AP-1 activity and tumor promoter induced neoplastic transformation. Basal and induced levels of c-Jun mRNA and protein are elevated in P+ cells compared to P- cells, whereas levels of other Jun family members are equal in P+ and P- cells, as are levels of c-Fos, Fra-1 and Fos B. However, levels of a novel protein species immunoprecipitated by anti-Fra-1 antibodies, and which we designate as """"""""Fra-1 related protein"""""""" or Fra-1 RP, are induced by tumor promoting agents in P- cells but not P+ cells. c-Jun and Fra-1 form a complex in JB6 cells to which Fra-1 RP may be bound via c-Jun. Currently, we are engaged in detailed characterization of Fra-1 RP and its association with the AP-1 transcription complex.
