Figure 2
Active canonical WNT signaling (as determined by nuclear β-catenin) stratifies the four murine colon tumor models into two groups. (a) Hierarchical clustering of gene transcripts separates the four models into two groups. The upper panel shows 1,798 gene transcripts identified as differentially expressed among any of the four mouse tumor models (Kruskal-Wallis test + Student-Newman-Keuls test + FDR < 5.10-5). Results demonstrate that AOM (A) and ApcMin/+ (M) tumors are transcriptionally more similar to each other than to tumors from Smad3-/- (S) and Tgfb1-/-; Rag2-/- (T) mice. Five clusters have been identified (C1-C5) that correspond to the K-means functional clusters listed in Table 1. Please refer to Table 1 for an in-depth description of the functional classification of the genes found in these clusters. The lower panel illustrates the extent of the similarity between A/M and S/T tumors by identifying the top-ranked 1,265 transcripts of the 1,798 that were higher or lower in the two tumor super-groups (rank based on Wilcoxon-Mann-Whitney test for between-group differences with a FDR < 5.10-5 cutoff). Up-regulated transcripts in A/M tumors are highly enriched for genes associated with canonical WNT signaling activity, cell proliferation, chromatin remodeling, cell cycle progression and mitosis; transcripts over-expressed in S/T tumors are highly enriched for genes related to immune and defense responses, endocytosis, transport, oxidoreductase activity, signal transduction and metabolism. (b) Representative histologies for each of the four tumor models. The lower panel illustrates the model-dependent localization of β-catenin. Tumors from M (bottom left) and A (not shown) mice exhibited prominent nuclear β-catenin accumulation and reduced cell surface staining. Conversely, tumors from S (bottom right) and T(not shown) mice exhibited retention of plasma membrane β-catenin immunoreactivity. A and M in top panel 100× magnification; S and T 200× magnification. M and S in lower panel both 400× magnification.