Tumor-promoting phorbol ester and activated Ha-ras synergistically reduce the interleukin 3 requirement in a mast cell line.
Infection of the bone marrow-derived mast cell line PB-3c with a retrovirus carrying oncogenic c-Ha-ras or v-Ha-ras reduced the interleukin 3 (IL-3) growth requirement and induced a state of tumorigenicity. In contrast, normal c-Ha-ras had no effect on the IL-3 requirement of this cell line nor did the cells become tumorigenic. A factor reduction similar to that caused by activated Ha-ras was transiently obtained with 12-O-tetradecanoylphorbol-13-acetate in the PB-3c cells expressing normal c-Ha-ras. The analogous stimulation of protein kinase C (PKC) in PB-3c cells producing oncogenic Ha-ras led to an additional reduction of the IL-3 requirement during the first 24 h. In the absence of IL-3, the prolonged exposure of the cells to 12-O-tetradecanoylphorbol-13-acetate for 72 h resulted in a stimulation of growth when activated but not when normal Ha-ras was expressed. PB-3c cell lines expressing activated Ha-ras neither revealed differences in the amounts nor in the subcellular distribution of PKC activity but displayed elevated levels of immunoreactive beta-PKC compared to the parental PB-3c cells. Upon 12-O-tetradecanoylphorbol-13-acetate treatment, a protracted down-regulation of the immunodetectable alpha-PKC as well as constitutively high levels of c-fos mRNA were observed when oncogenic Ha-ras was expressed. These data suggest the involvement of specific PKC subtypes and of c-fos in the reduction of the IL-3 requirement caused by activated Ha-ras in this particular hematopoietic cell line.
Imber
R
R
Molecular Tumorbiology, Department of Research, University Clinic Medical School, Basel, Switzerland.
Fabbro
D
D
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras; D005822:Genetic Vectors; D007377:Interleukin-3 / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015183:Restriction Mapping; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection
D007377:Interleukin-3; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate