Embryonic stem (ES) cells lacking functional c-jun: consequences for growth and differentiation, AP-1 activity and tumorigenicity.
The proto-oncogene c-jun encodes the major component of the transcription factor AP-1 and is thought to have important functions in cell proliferation and differentiation as well as in the cellular response to a variety of external stimuli. To investigate directly the role of c-jun in growth, differentiation and tumorigenicity we generated mouse embryonic stem (ES) cell lines in which both copies of the c-jun gene have been inactivated by homologous recombination. The disruption of both copies of the c-jun gene had no apparent effect on ES cell viability, growth rate and in vitro differentiation potential. Transcriptional activation of the c-jun, junB and c-fos genes following TPA/serum induction was unaffected and efficient transactivation of AP-1 reporter constructs was demonstrated in these cells. Remarkably, subcutaneous injection of ES cells lacking c-Jun into syngeneic mice led to a drastic reduction in the formation of teratocarcinomas. We propose that whereas most of the functions of c-Jun in ES cells appear to be complemented by other Jun proteins in vitro, functional c-Jun protein is essential for efficient tumor growth in vivo.
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun; D005822:Genetic Vectors; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D013724:Teratoma / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012313:RNA; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate