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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Female
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Genes, erbB-2 / genetics*
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Genes, p53 / genetics*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Muscle Neoplasms / genetics*
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Muscle Neoplasms / metabolism
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Muscle, Skeletal / pathology
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Mutation*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Receptor, ErbB-2 / biosynthesis
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Receptor, ErbB-2 / genetics
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Rhabdomyosarcoma / genetics*
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Rhabdomyosarcoma / metabolism
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
Substances
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RNA, Messenger
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Tumor Suppressor Protein p53
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Receptor, ErbB-2