Reversible abrogation of IL-3 dependence by an inducible H-ras oncogene.
Immortalized, interleukin-3 (IL-3)-dependent mouse mast cells (PB-3c) were transfected with a human activated c-H-ras gene under the transcriptional control of the mouse mammary tumor virus long terminal repeat. Addition of increasing amounts of dexamethasone resulted in a concentration-dependent increase in expression of the H-ras oncogene. The elevation of p21 ras protein concentrations was paralleled by progressive growth of the transfectants in the absence of exogenous IL-3, leading to complete abrogation of growth-factor requirement at high p21ras levels. The maintenance of the IL-3-independent state required the continuous expression of the H-ras oncogene, since dexamethasone removal was followed by rapid cell death. Expression of the H-ras oncogene induced PB-3c cells to produce IL-3 and granulocyte-macrophage colony-stimulating factor, suggesting that their IL-3-independent proliferation may be due to an autocrine mechanism.
Andrejauskas
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E
Institute for Medical Microbiology, University of Basel, Switzerland.
Moroni
C
C
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004560:Electricity; D011905:Genes, ras / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis / Q000502:physiology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000502:physiology*; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015689:Oncogene Protein p21(ras)