Enhanced synthesis and stabilization of Mr 68,000 protein in transformed BALB/c-3T3 cells: candidate for restriction point control of cell growth.
We have proposed that transformation of cells to tumorigenicity by chemical carcinogens can depend upon stabilization of a protein responsible for growth regulation. Cell kinetic experiments in which normal and benzo[a]pyrene-transformed BALB/c-3T3 cells were pulsed with cycloheximide indicated this protein should have a half-life of a few hours in normal cells and be considerably more stable in transformed cells [Campisi, J., Medrano, E. E., Morreo, G. & Pardee, A. B. (1982) Proc. Natl. Acad. Sci. USA 79, 436-440]. A protein with these properties has not yet been reported. We have searched for such a protein using two-dimensional electrophoresis to resolve protein from cells labeled with [35S]methionine. Among approximately 1,000 proteins that were resolved in these gels, we have found one that has a greater rate of synthesis and stability in benzo[a]pyrene-transformed than in untransformed cells. This result satisfies a necessary prediction of our labile protein hypothesis. We suggest that this protein could be important in determining the loss of growth regulation in these tumor cells.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism
D001580:Benzopyrenes; D002273:Carcinogens; D009363:Neoplasm Proteins; D001564:Benzo(a)pyrene