Aberrant transactivation of a certain set of target genes by the beta-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor complexes has been implicated in the process of intestinal epithelial cells entering early colorectal carcinogenesis. A rat intestinal epithelial cell line IEC6 became elongated, extended protrusions at cell periphery, and increased stress fibers and focal contacts upon the induction of beta-catenin protein stabilized by deletion of the N-terminal glycogen synthase kinase-3beta (GSKbeta) phosphorylation sites (beta-catenin DeltaN89). We used the GeneChiptrade mark oligonucleotide microarray system to examine approximately 24 000 genes and identified 13 genes whose expression was altered during the course of this morphological transformation. Those genes included known negative regulators of the Wnt signaling pathway, Sfrp4 and Axin2; extracellular matrix and related molecule, Hxb and Crtl1; cell adhesion and cytoskeletal proteins, Podxl, Igaf4, and Itab6; and molecules involved in the insulin and insulin-like growth factor (IGF) signaling pathways, Enpp1, Igfbp2, and Sgk. We report the finding that insulin-like growth factor-binding protein-2 (IGFBP2) is a direct target gene of the beta-catenin and TCF/LEF complexes. The IGFBP2 protein interacts with integrins. Disruption of the multigene network system regulating cell adhesion and cytoskeleton may be crucial in the initiation of colorectal carcinogenesis.
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C2: Curated CGP: Chemical and Genetic Perturbations
