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

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

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.

Year of Publication
2007
Journal
Proc Natl Acad Sci U S A
Volume
104
Issue
45
Pages
17771-6
Date Published
2007 Nov 06
ISSN
0027-8424
URL
DOI
10.1073/pnas.0708476104
PubMed ID
17978178
PubMed Central ID
PMC2077015
Links
Grant list
P01 CA089021 / CA / NCI NIH HHS / United States