Defective induction of Jun and Fos-related proteins in phorbol ester-resistant EL4 mouse thymoma cells.
Treatment of sensitive EL4 mouse thymoma cells with phorbol esters causes growth inhibition, adherence to substrate and production of several lymphokines including Interleukin 2. Resistant cells lack all of these responses. Since production of Interleukin 2 mRNA is dependent on protein synthesis, and the Interleukin 2 gene has a phorbol ester responsive element, we examined both cell lines for expression of the various Jun and Fos species which bind to this element. Phorbol ester induced c-fos, jun-B, and jun-D RNAs within 20 min in both cell lines. Fos-B was similarly induced in sensitive cells but induction was delayed and greatly enhanced in resistant cells. C-jun RNA induction was detected only in sensitive cells. Western analysis confirmed the induction of c-Jun and a Fos-related protein in sensitive cells only. Southern analysis indicated that both cell lines contain c-jun and fra-1 genes. These results suggest that defective induction of c-Jun and/or Fos-related proteins may contribute to the absence of phorbol ester-induced lymphokine production in resistant EL4 cells.
Jensen
D E
DE
Department of Pharmacology, University of Virginia, Charlottesville 22908.
Frankis
R C
RC
Sando
J J
JJ
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004351:Drug Resistance; D015870:Gene Expression; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010703:Phorbol Esters / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012313:RNA / Q000096:biosynthesis; D013945:Thymoma / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D015345:Oligonucleotide Probes; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D012313:RNA; D004247:DNA