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

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Sekine S,Shibata T,Sakamoto M,Hirohashi S

doi

10.1038/sj.onc.1205756

subject

Has Abstract

pub_date

2002-08-29 00:00:00

pages

5906-11

issue

38

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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