title: Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice.
abstract: Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.
authors.affiliation: Department of Cell Biology, Fraunhofer Institut für Toxikologie und Molekularbiologie, Hannover, Germany.
authors.forename: R R
authors.initials: RR
authors.lastname: Tönjes
authors.forename: J
authors.initials: J
authors.lastname: Löhler
authors.forename: J F
authors.initials: JF
authors.lastname: O'Sullivan
authors.forename: G F
authors.initials: GF
authors.lastname: Kay
authors.forename: G H
authors.initials: GH
authors.lastname: Schmidt
authors.forename: W
authors.initials: W
authors.lastname: Dalemans
authors.forename: A
authors.initials: A
authors.lastname: Pavirani
authors.forename: D
authors.initials: D
authors.lastname: Paul
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016259:Genes, myc; D008113:Liver Neoplasms / Q000209:etiology*; D008114:Liver Neoplasms, Experimental / Q000209:etiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008934:Mitogens; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*
chemical_list: D008934:Mitogens; D016271:Proto-Oncogene Proteins c-myc; D004815:Epidermal Growth Factor