The up-regulated signature in tumors from ApcMin/+ (M) and AOM (A) models (cluster C6, Figure 2) is enriched with genes associated with the activation of the canonical WNT signaling pathway, as determined by nuclear β-catenin positivity. (a) Schematic diagram of the canonical WNT signaling pathway showing elements present in cluster C6 (gene symbols with gray background). Key elements of this pathway (Ctnnb1, Lef1, Tcf and Myc) are outlined in blue. (b) Relative gene expression for MYC and SOX4 is plotted for individual murine and human tumors. The relative expression level of MYC and SOX4 is normalized to adult colon. Note that whereas Sox4, a canonical WNT target gene, is expressed at high levels in all human CRCs, A/M tumors and during embryonic mouse colon development, it is not expressed in Smad3-/- (S) and Tgfb1-/-; Rag2-/- (T) tumors (black). In contrast, MYC is over-expressed in all human and murine tumors and during colonic embryonic development (red), irrespective of the activation of canonical WNT signaling, as determined by nuclear β-catenin positivity (Figure 2). Tissue groups: as above and: nAC-m, normal adult mouse colon; nAC-h, normal adult human colon; Dev, developing mouse colon.