Myc-driven murine prostate cancer shares molecular features with human prostate tumors.
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.
Ellwood-Yen
Katharine
K
Department of Medicine, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Graeber
Thomas G
TG
Wongvipat
John
J
Iruela-Arispe
M Luisa
ML
Zhang
JianFeng
J
Matusik
Robert
R
Thomas
George V
GV
Sawyers
Charles L
CL
D000230:Adenocarcinoma / Q000503:physiopathology*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016259:Genes, myc / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D009919:Orchiectomy; D011467:Prostate / Q000503:physiopathology*; D019048:Prostatic Intraepithelial Neoplasia / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1; D014157:Transcription Factors / Q000378:metabolism
D000728:Androgens; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; C102837:Nkx3-1 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C496634:PIM1 protein, human; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1