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Proc Natl Acad Sci U S A DOI:10.1073/pnas.0708476104

Identification of prostate cancer modifier pathways using parental strain expression mapping.

Publication TypeJournal Article
Year of Publication2007
AuthorsXu, Q, Majumder, PK, Ross, K, Shim, Y, Golub, TR, Loda, M, Sellers, WR
JournalProc Natl Acad Sci U S A
Date Published2007 Nov 06
KeywordsAnimals, Cell Division, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genetic Variation, Genome, Humans, Male, Mice, Mice, Inbred Strains, Prostatic Neoplasms, RNA, Messenger, Species Specificity, Transcription, Genetic

Inherited genetic risk factors play an important role in cancer. However, other than the Mendelian fashion cancer susceptibility genes found in familial cancer syndromes, little is known about risk modifiers that control individual susceptibility. Here we developed a strategy, parental strain expression mapping, that utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses to directly identify candidate germ-line modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and, specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with the findings in the murine models, in multiple human prostate expression data set, we found that enrichment of glycolysis pathways in normal tissues was associated with decreased rates of cancer recurrence after prostatectomy. Together, these data suggest that parental strain expression mapping can directly identify germ-line modifier pathways of relevance to human disease.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID17978178
PubMed Central IDPMC2077015
Grant ListP01 CA089021 / CA / NCI NIH HHS / United States