Large-scale deployment of embryonic gene programming in human and murine colon cancer: a new target for intervention.

ABSTRACT: Goal of the experiment: To identify and understand the overall transcriptional programming of human colorectal cancer tumors by evaluating gene expression profiles of tumors from four murine models, and comparing and contrasting these to the developing stages of the mouse embryonic colon. Experiment description: Colorectal cancer results from multiple genetic and epigenetic events that produce variable histologies and clinical outcomes. To identify gene regulatory programs that underlie colon tumorigenesis, we profiled gene expression in 39 mouse colon tumors from four independent mouse models and compared this to mouse colon embryonic development, as well as with 100 human colon carcinomas. Here, we report a striking recapitulation of embryonic patterns of gene expression in both mouse and human colon tumors. All four of the mouse colon tumor models exhibited large-scale activation of embryonic gene expression signatures. The two nuclear beta-catenin-positive mouse tumors (azoxymethane-treated [AOM] and ApcMin/+), exhibited strong activation of genes characteristic of those expressed in the earliest embryonic stages, while tumors from two other models (Smad3-/- and Tgfb1-/- x Rag2-/-) exhibited lower activation of early stage-specific genes but substantial expression of general embryonic colon genes. Human colon cancer cases over-expressed genes characteristic of both early and late embryonic stages. Examining tumor gene expression through the lens of development has revealed an extensive network of therapeutic targets for cancer control. Keywords: Colorectal cancer, tumor, animal models, development, comparative genomics, orthologenome

ORGANISM(S): Homo sapiens

PROVIDER: GSE5206 | GEO | 2006/07/01

SECONDARY ACCESSION(S): PRJNA104289

REPOSITORIES: GEO