title: The human alphaE-catenin gene CTNNA1: mutational analysis and rare occurrence of a truncated splice variant.
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.
authors: Molecular Cell Biology Unit, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (V.I.B.), Ghent University, Ledeganckstraat 35, B-9000, Ghent, Belgium.
authors: Griet
authors: G
authors: Vanpoucke
authors: Friedel
authors: F
authors: Nollet
authors: Sabine
authors: S
authors: Tejpar
authors: Jean-Jacques
authors: JJ
authors: Cassiman
authors: Frans
authors: F
authors: van Roy
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D051178:alpha Catenin