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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
Author(s) -
Bernstein Lori R.,
Bravo Rodrigo,
Colburn Nancy H.
Publication year - 1992
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940060308
Subject(s) - biology , immunoprecipitation , tumor promotion , 12 o tetradecanoylphorbol 13 acetate , promotion (chess) , microbiology and biotechnology , biochemistry , carcinogenesis , phosphorylation , gene , protein kinase c , phorbol ester , politics , political science , law
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. © 1992 Wiley‐Liss, Inc.