Beta-catenin mutations in cell lines established from human colorectal cancers

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

Research output: Contribution to journalArticlepeer-review

Abstract

beta-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the beta-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of beta-catenin by reverse transcriptase-PCR (RT-PCR) and direct sequencing of 23 human colorectal cancer cell lines from 21 patients. In two cell lines, there was apparent instability of the beta-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 beta-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 beta-catenin with alpha-catenin and APC were detectable. In SW48 and HCA 46, however, we did not detect complexes of beta-catenin protein with alpha-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 beta-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)10330-4
Number of pages5
JournalProceedings of the National Academy of Sciences
Volume94
Issue number19
DOIs
Publication statusPublished - 16 Sep 1997

Keywords

  • Amino Acid Sequence
  • Blotting, Western
  • Codon
  • Cytoskeletal Proteins/genetics
  • DNA, Complementary
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Polymorphism, Single-Stranded Conformational
  • Precipitin Tests
  • RNA, Messenger/genetics
  • Trans-Activators
  • Tumor Cells, Cultured
  • beta Catenin

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