Abstract
Increased Myc gene copy number is observed in human prostate cancer. To define Myc's functional role, we generated transgenic mice expressing human c-Myc in the mouse prostate. All mice developed murine prostatic intraepithelial neoplasia followed by invasive adenocarcinoma. Microarray-based expression profiling identified a Myc prostate cancer expression signature, which included the putative human tumor suppressor NXK3.1. Human prostate tumor databases revealed modules of human genes that varied in concert with the Myc prostate cancer signature. This module includes the Pim-1 kinase, a gene known to cooperate with Myc in tumorigenesis, and defines a subset of human, "Myc-like" human cancers. This approach illustrates how genomic technologies can be applied to mouse cancer models to guide evaluation of human tumor databases.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / physiopathology*
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Androgens / metabolism
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Animals
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / physiology
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Genes, myc / genetics
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Genes, myc / physiology*
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Homeodomain Proteins / metabolism
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Humans
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Male
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Mice
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Mice, Transgenic
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Neovascularization, Pathologic
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Orchiectomy
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Prostate / physiopathology*
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Prostatic Intraepithelial Neoplasia / physiopathology
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Prostatic Neoplasms / physiopathology*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-pim-1
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Transcription Factors / metabolism
Substances
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Androgens
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Homeodomain Proteins
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NKX3-1 protein, human
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Nkx3-1 protein, mouse
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Proto-Oncogene Proteins
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Transcription Factors
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PIM1 protein, human
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Pim1 protein, mouse
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-pim-1