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

Shigeki Sekine, Tatsuhiro Shibata, Michiie Sakamoto, Setsuo Hirohashi

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 hi 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.

Original languageEnglish
Pages (from-to)5906-5911
Number of pages6
JournalOncogene
Volume21
Issue number38
DOIs
Publication statusPublished - 2002 Aug 29
Externally publishedYes

Fingerprint

Catenins
Colonic Neoplasms
Clone Cells
Phenotype
Cell Line
Alleles
TCF Transcription Factors
Colorectal Neoplasms
Genes
Growth
Homologous Recombination
Adhesives
Down-Regulation
Mutation
Serum

Keywords

  • β-catenin
  • Colorectal carcinoma
  • Gene targeting
  • Mutation
  • TCF/LEF-dependent transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116 : Preservation of its malignant phenotype. / Sekine, Shigeki; Shibata, Tatsuhiro; Sakamoto, Michiie; Hirohashi, Setsuo.

In: Oncogene, Vol. 21, No. 38, 29.08.2002, p. 5906-5911.

Research output: Contribution to journalArticle

Sekine, Shigeki ; Shibata, Tatsuhiro ; Sakamoto, Michiie ; Hirohashi, Setsuo. / Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116 : Preservation of its malignant phenotype. In: Oncogene. 2002 ; Vol. 21, No. 38. pp. 5906-5911.
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