Comparison of mouse pro-1 and pro-2 transfectants for responses to tumor promoters and antipromoters.
A previous report demonstrated that mouse JB6 cells transformed to promotion sensitive (P+) phenotype by transfection with an activated promotion sensitivity (pro) gene showed both evidence for the presence of the transfected gene and sensitivity to phorbol ester induced transformation similar to that observed in parental P+ cells. In addition, pro-1 and pro-2 transfectants were similar to each other in phorbol ester response. The current report extends these findings to ask whether pro-1 or pro-2 transfectants are also sensitive to promotion of transformation by other classes of tumor promoters such as epidermal growth factor (EGF), lanthanides, and phthalate esters and to inhibition of phorbol ester promoted transformation by several classes of antipromoters. The results showed that both pro-1 and pro-2 transfectants resembled parental P+ cells in sensitivity to promotion of anchorage independent transformation by lanthanides and by diethylhexylphthalate. In addition both pro-1 and pro-2 transfectants showed inhibition of phorbol ester induced transformation by antipromoters ganglioside GT1b, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and forskolin. Thus the pathways implicated by these inducers and inhibitors of transformation appear similar to those implicated for parental P+ cells and similar when controlled by pro-1 or pro-2. The single differential response was that of EGF-induced transformation. pro-2 transfectants but not pro-1 transfectants were sensitive to EGF-induced neoplastic transformation. The nonresponsiveness could not be attributed to lack of EGF receptors since 125I-EGF binding to pro-1 transfectants was similar to that for pro-2 transfectants and parental P+ cells. Thus pro genes transfer responsiveness to a C-kinase mediated promotion of transformation pathway and to putatively non-C kinase pathways triggered by lanthanides or phthalate esters, but not necessarily to an EGF receptor kinase mediated pathway.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D004533:Egtazic Acid / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate; D014162:Transfection
D004533:Egtazic Acid; D004815:Epidermal Growth Factor; D004051:Diethylhexyl Phthalate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate