title: Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53.
abstract: The transcription factor c-Jun mediates several cellular processes, including proliferation and survival, and is upregulated in many carcinomas. Liver-specific inactivation of c-Jun at different stages of tumor development was used to study its role in chemically induced hepatocellular carcinomas (HCCs) in mice. The requirement for c-jun was restricted to early stages of tumor development, and the number and size of hepatic tumors was dramatically reduced when c-jun was inactivated after the tumor had initiated. The impaired tumor development correlated with increased levels of p53 and its target gene noxa, resulting in the induction of apoptosis without affecting cell proliferation. Primary hepatocytes lacking c-Jun showed increased sensitivity to TNF-alpha-induced apoptosis, which was abrogated in the absence of p53. These data indicate that c-Jun prevents apoptosis by antagonizing p53 activity, illustrating a mechanism that might contribute to the early stages of human HCC development.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr. Bohrgasse 7, A-1030, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Eferl
authors.forename: Romeo
authors.initials: R
authors.lastname: Ricci
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Rainer
authors.initials: R
authors.lastname: Zenz
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: David
authors.forename: Martina
authors.initials: M
authors.lastname: Rath
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53