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 journalArticle

96 Citations (Scopus)

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
StatePublished - Aug 1 1997

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Catenins
Growth
Genes
Neoplasms
Cadherins
Tumor Suppressor Genes
Nude Mice
Cell Adhesion
Cytoplasm
Proteins
Binding Sites
Carcinoma
Amino Acids
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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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.",
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Expression of wild-type α-catenin protein in cells with a mutant α- catenin gene restores both growth regulation and tumor suppressor activities. / Bullions, Linda C.; Notterman, Daniel A.; Chung, Lorinda S.; Levine, Arnold J.

In: Molecular and cellular biology, Vol. 17, No. 8, 01.08.1997, p. 4501-4508.

Research output: Contribution to journalArticle

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AB - 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.

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