title: Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice.
abstract: Rhabdomyosarcomas derive from the skeletal muscle lineage and harbor a variety of genetic and molecular lesions. However, it is not clear which molecular alterations have a pathogenetic role. We show that activation of the HER-2/neu oncogene coupled with inactivation of the oncosuppressor gene p53 causes rhabdomyosarcoma in mice. At the age of 11-21 weeks, all male mice carrying both genetic lesions developed embryonal rhabdomyosarcomas expressing desmin, myosin, and insulin-like growth factor-II, in the genitourinary tract. Our findings led to the hypothesis that the interaction between HER family genes and the p53 pathway might be involved in the origin of human rhabdomyosarcoma.
authors.affiliation: Cancer Research Section, Department of Experimental Pathology, University of Bologna, I-40126 Bologna.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nanni
authors.forename: Giordano
authors.initials: G
authors.lastname: Nicoletti
authors.forename: Carla
authors.initials: C
authors.lastname: De Giovanni
authors.forename: Stefania
authors.initials: S
authors.lastname: Croci
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Lorena
authors.initials: L
authors.lastname: Landuzzi
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Piero
authors.initials: P
authors.lastname: Musiani
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D000483:Alleles; D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018734:Genes, erbB-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019042:Muscle Neoplasms / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53