Target disruption of the mutant beta-catenin gene in colon cancer cell line HCT116: preservation of its malignant phenotype.
Most colorectal carcinomas harbor genetic alterations that result in stabilization of beta-catenin. A colorectal carcinoma cell line, HCT116, which has both mutated and wild-type beta-catenin genes, was engineered by homologous recombination to investigate the significance of beta-catenin gene mutation. As expected, the mutant allele-targeted clones showed decreased beta-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 beta-catenin stabilization affects some biological characteristics including adhesive properties, it may not have growth-promoting effects at least in some colorectal carcinomas.
Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Shigeki
S
Sekine
Tatsuhiro
T
Shibata
Michiie
M
Sakamoto
Setsuo
S
Hirohashi
D000818:Animals; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin