Ras oncogenes amplify lymphokine (interleukin 3, granulocyte-macrophage colony-stimulating factor) induction by calcium ionophore.
Interleukin 3 (IL-3) expression in PB-3c mastocytes is transiently induced in vitro by treatment with the drug A23187, a calcium ionophore, or constitutively following ras-dependent transformation in vivo. While the mechanism of oncogenically induced IL-3 expression is not clear, A23187-mediated lymphokine mRNA accumulation is primarily the result of calcium-dependent mRNA stabilization. We investigated whether the expression of various ras alleles influenced IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA induction by A23187. It was found that activated forms of ras potentiated ionophore-mediated lymphokine mRNA accumulation. This enhancement involves a post-transcriptional mechanism, as ionophore-induced lymphokine mRNAs are significantly more stable in ras oncogene-expressing lines than in the control line. We propose that one way by which ras genes exert their oncogenic potential is by extending the half-life of short-lived growth factor mRNAs.
Hahn
S
S
Institut für Mediizinische Mikrobiologie, Universität Basel, Switzerland.
Wodnar-Filipowicz
A
A
Nair
A P
AP
Moroni
C
C
D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005784:Gene Amplification / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D007377:Interleukin-3; D012333:RNA, Messenger; D003609:Dactinomycin; D000001:Calcimycin; D012313:RNA; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor