Expression of Wild-Type α-Catenin Protein in Cells with a Mutant α-Catenin Gene Restores Both Growth Regulation and Tumor Suppressor Activities
- 1 August 1997
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 17 (8) , 4501-4508
- https://doi.org/10.1128/mcb.17.8.4501
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, alpha-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 alpha-catenin protein lacking the extreme N terminus of the wild-type protein. The altered form of alpha-catenin expressed in Ov2008 cells fails to bind efficiently to beta-catenin and is localized in the cytoplasm. Deletion mapping has localized the beta-catenin binding site on alpha-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 alpha-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 alpha-catenin expression in Ov2008 cells injected into nude mice attenuated the ability of these cells to form tumors. These observations support the classification of alpha-catenin as a growth-regulatory and candidate tumor suppressor gene.Keywords
This publication has 40 references indexed in Scilit:
- Expression of cadherins and alpha-catenin in primary epithelial tumors of the liverGastroenterology, 1996
- Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.The Journal of cell biology, 1994
- Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly.The Journal of cell biology, 1994
- Frequent Loss of α Catenin Expression in Scirrhous Carcinomas with Scattered Cell GrowthJapanese Journal of Cancer Research, 1994
- Cloning of the Human α-Catenin cDNA and Its Aberrant mRNA in a Human Cancer Cell LineBiochemical and Biophysical Research Communications, 1993
- Regulation of embryonic cell adhesion by the cadherin cytoplasmic domainPublished by Elsevier ,1992
- Transmembrane molecular assemblies regulated by the greater cadherin familyCurrent Opinion in Cell Biology, 1991
- Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor roleCell, 1991
- CADHERINS: A MOLECULAR FAMILY IMPORTANT IN SELECTIVE CELL-CELL ADHESIONAnnual Review of Biochemistry, 1990
- Initiation of translation at internal AUG codons in mammalian cellsNature, 1984