β-Catenin mutations in cell lines established from human colorectal cancers

M. Ilyas, I. P M Tomlinson, A. Rowan, M. Pignatelli, W. F. Bodmer

Research output: Contribution to journalArticle

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Abstract

β-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the β-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of β-catenin by reverse transcriptase- PCR (RT-PCR) and direct sequencing of 2,3 human colorectal cancer cell lines from 21 patients. In two cell lines, there was apparent instability of the β-catenin mRNA. Five different mutations (26%) were found in the remaining 21cell lines (from 19 patients). A three-base deletion (codon 45) was identified in the cell line HCT 116, whereas cell lines SW 48, HCA 46, CACO 2, and Colo 201 each contained single-base missense mutations (codons 33, 183, 245, and 287, respectively). All 23 cell lines had full-length β- catenin protein that was detectable by Western blotting and that coprecipitated with E-cadherin. In three of the cell lines with CTNNB1 mutations, complexes of β-catenin with α-catenin and APC were detectable. In SW48 and HCA 46, however, we did not detect complexes of β-catenin protein with α-catenin and APC, respectively. These results show that selection of CTNNB1 mutations occurs in up to 26% of colorectal cancers from which cell lines are derived. In these cases, mutation selection is probably for altered β-catenin function, which may significantly alter intracellular signaling and intercellular adhesion and may serve as a complement to APC mutations in the early stages of tumorigenesis.

Original languageEnglish
Pages (from-to)10330-10334
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number19
DOIs
Publication statusPublished - Sep 16 1997
Externally publishedYes

Fingerprint

Catenins
Colorectal Neoplasms
Cell Line
Mutation
Codon
HCT116 Cells
RNA Stability
Missense Mutation
Cadherins
Reverse Transcriptase Polymerase Chain Reaction
Carcinogenesis
Western Blotting

Keywords

  • CTNNB1
  • Intestinal cancer
  • Sequencing

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

β-Catenin mutations in cell lines established from human colorectal cancers. / Ilyas, M.; Tomlinson, I. P M; Rowan, A.; Pignatelli, M.; Bodmer, W. F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 19, 16.09.1997, p. 10330-10334.

Research output: Contribution to journalArticle

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