Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice.
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.
Nanni
Patrizia
P
Cancer Research Section, Department of Experimental Pathology, University of Bologna, I-40126 Bologna.
Nicoletti
Giordano
G
De Giovanni
Carla
C
Croci
Stefania
S
Astolfi
Annalisa
A
Landuzzi
Lorena
L
Di Carlo
Emma
E
Iezzi
Manuela
M
Musiani
Piero
P
Lollini
Pier-Luigi
PL
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
D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53