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  • The human αE-catenin gene CTNNA1: mutational analysis and rare occurrence of a truncated splice variant
  • Add time:09/07/2019         Source:sciencedirect.com

    Abnormal expression of the αE-catenin protein, a component of the E-cadherin/catenin cell adhesion complex, is frequently observed in human cancer cells. An inverse correlation between αE-catenin expression and tumor malignancy can be of prognostic value. Mutations of the αE-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 αE-catenin mutational analysis. On the basis of our genomic characterization data, we found that the previously reported alternative splicing of the αE-catenin gene actually generates a frame-shift, resulting in a truncated αE-catenin protein. This finding is unlike the other α-catenin family members αN-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 αE-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 α-catenin/vinculin family.

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