Expression of wild-type α-catenin protein in cells with a mutant α- catenin gene restores both growth regulation and tumor suppressor activities

Linda C. Bullions, Daniel A. Notterman, Lorinda S. Chung, Arnold J. Levine

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Recent studies indicate that disruption of the E-cadherin-mediated cell- cell adhesion system is frequently associated with human cancers of epithelial origin. Reduced levels of both E-cadherin and the associated protein, α-catenin, have been reported in human tumors. This report describes the characterization of a human ovarian carcinoma-derived cell line (Ov2008) which expresses a novel mutant form of the α-catenin protein lacking the extreme N terminus of the wild-type protein. The altered form of α-catenin expressed in Ov2008 cells fails to bind efficiently to β-catenin and is localized in the cytoplasm. Deletion mapping has localized the β- catenin binding site on α-catenin between amino acids 46 and 149, which encompasses the same region of the protein that is deleted in the Ov2008 variant. Restoration of inducible expression of the wild-type α-catenin protein in these cells caused them to assume the morphology typical of an epithelial sheet and retarded their growth in vitro. Additionally, the induction of α-catenin expression in Ov2008 cells injected into nude mice attenuated the ability of these cells to forth tumors. These observations support the classification of α-catenin as a growth-regulatory and candidate tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)4501-4508
Number of pages8
JournalMolecular and cellular biology
Volume17
Issue number8
DOIs
StatePublished - Aug 1997

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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