The human alphaE-catenin gene CTNNA1: mutational analysis and rare occurrence of a truncated splice variant

Biochim Biophys Acta. 2002 Apr 12;1574(3):262-8. doi: 10.1016/s0167-4781(01)00378-5.

Abstract

Abnormal expression of the alphaE-catenin protein, a component of the E-cadherin/catenin cell adhesion complex, is frequently observed in human cancer cells. An inverse correlation between alphaE-catenin expression and tumor malignancy can be of prognostic value. Mutations of the alphaE-catenin gene, CTNNA1, were described in several human cancer cell lines and were found to result in aberrant cell adhesion. We have developed a polymerase chain reaction/single-strand conformation polymorphism-based method for mutation analysis of this gene in human tumor DNA. This approach enabled us to identify several polymorphisms in a set of desmoid tumors, demonstrating that this method is suitable for alphaE-catenin mutational analysis. On the basis of our genomic characterization data, we found that the previously reported alternative splicing of the alphaE-catenin gene actually generates a frame-shift, resulting in a truncated alphaE-catenin protein. This finding is unlike the other alpha-catenin family members alphaN-catenin and vinculin, which show in-frame alternative inserts. Furthermore, real-time quantitative reverse transcriptase-PCR analysis did not reveal relevant expression levels of this alternatively spliced alphaE-catenin variant neither in any human tissue or cell line tested, nor at any mouse developmental stage tested. Thus, contrary to previous notions, alternative splicing with in-frame insertion nearby the C-terminal end of the protein is not a general feature for all members of the alpha-catenin/vinculin family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cytoskeletal Proteins / genetics*
  • DNA, Neoplasm / analysis
  • Exons
  • Humans
  • Introns
  • Mice
  • Mutation
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Tumor Cells, Cultured
  • alpha Catenin

Substances

  • CTNNA1 protein, human
  • Ctnna1 protein, mouse
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • alpha Catenin