12-O-tetradecanoylphorbol-13-acetate--induced levels of AP-1 proteins: a 46-kDa protein immunoprecipitated by anti-fra-1 and induced in promotion-resistant but not promotion-sensitive JB6 cells.
Neoplastic transformation and transcriptional activation by activator protein-1 (AP-1) complex are stimulated by tumor-promoting agents in promotion-sensitive (P+) but not promotion-resistant (P-) mouse epidermal JB6 cells in culture. This implicates AP-1 as a specific regulator of signal transduction pathways in the promotion phase of neoplastic transformation. We therefore hypothesized that the defective P- responsiveness may be due to limiting levels of AP-1 protein components in those cells. In this investigation, steady-state levels of AP-1 protein components were measured by immunoprecipitating proteins from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated P+ and P- cells to discern what may limit the AP-1 response. Whereas the AP-1 proteins junB, junD, and fosB did not show differential basal or TPA-inducible levels in P+ and P- cells, a 46-kDa species precipitated by anti-fra-1 antibody was TPA-inducible in P- cells but not in P+ cells, and c-jun protein was present at higher levels in TPA-treated and untreated P+ cells than in P- cells. These data raise the possibility that the 46-kDa fra-1-related protein may be a negative modulator of AP-1 activity and suggest that elevated levels of this 46-kDa species and limiting levels of c-jun may significantly impair AP-1 function or transformation response in P- cells or both.
Bernstein
L R
LR
Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
Bravo
R
R
Colburn
N H
NH
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013755:Tetradecanoylphorbol Acetate; D000099169:Fos-Related Antigen 1