Scientific Publications

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

Publication TypeJournal Article
AuthorsXu, Q., Majumder PK, Ross K., Shim Y., Golub T. R., Loda M., and Sellers WR
AbstractInherited 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.
Year of Publication2007
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue45
Pages17771-6
Date Published (YYYY/MM/DD)2007/11/06
ISSN Number0027-8424
DOI10.1073/pnas.0708476104
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/17978178?dopt=Abstract