Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116: preservation of its malignant phenotype

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Abstract
Most colorectal carcinomas harbor genetic alterations that result in stabilization of β-catenin. A colorectal carcinoma cell line, HCT116, which has both mutated and wild-type β-catenin genes, was engineered by homologous recombination to investigate the significance of β-catenin gene mutation. As expected, the mutant allele-targeted clones showed decreased β-catenin expression and downregulation of T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcription. Morphologically, targeted clones were only minimally altered under usual culture conditions, but under low serum conditions, mutant allele-targeted clones still grew in plane, in contrast to parental cell line and wild allele-targeted clones, which formed spheroids. The mutant allele-targeted clones showed no significant changes in growth rate and anchorage-independent growth in vitro, and displayed rather increased growth in vivo. Although β-catenin stabilization affects some biological characteristics including adhesive properties, it may not have growth-promoting effects at least in some colorectal carcinomas.