Tumor promoters induce the synthesis of a secreted glycoprotein in mouse skin and cultured primary mouse epidermal cells.
The effect of tumor promoters and anti-promoters on the synthesis and secretion of a 35,000 mol wt transformation-dependent secreted glycoprotein (MEP) by primary mouse epidermal cells has been investigated. MEP is synthesized and secreted at low levels by cultured epidermal basal cells. The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) induces a 3-fold increase in the synthesis of MEP as determined by quantitative immunoprecipitation from pulse-labeled cell extracts. This increase is maximal 6 h after treatment and parallels an increase in secretion of MEP measured by appearance of radiolabeled protein in the medium or by radioimmunoassay of culture supernatants. An increase in MEP synthesis is also observed in the skin of mice exposed to TPA. The phorbol ester antagonists retinoic acid, lidocaine and fluocinolone acetonide were examined to determine their effect on the synthesis and secretion of MEP. Of these agents, only fluocinolone acetonide affects MEP levels by suppressing the basal level of MEP synthesis but not its relative induction by TPA. These data suggest that the modifying effects of these three agents on tumor promotion are not mediated via an alteration in MEP synthesis per se is not sufficient for promotion.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000378:metabolism*; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D002273:Carcinogens; D006023:Glycoproteins; D013755:Tetradecanoylphorbol Acetate