@article{87161, keywords = {Animals, Base Sequence, Humans, Genes, Molecular Sequence Data, Trans-Activators, Amino Acid Sequence, Mice, Gene Expression, Tumor Cells, Cultured, Female, Cell Division, Breast Neoplasms, Epithelial Cells, Cell Adhesion, Cadherins, Cytoskeletal Proteins, Epithelium, Genes, Tumor Suppressor, alpha Catenin, beta Catenin, Carcinoma, Mice, Nude, Ovarian Neoplasms, Point Mutation}, author = {Bullions and Notterman and Chung and Levine}, title = {Expression of wild-type alpha-catenin protein in cells with a mutant alpha-catenin gene restores both growth regulation and tumor suppressor activities.}, 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. }, year = {1997}, journal = {Mol Cell Biol}, volume = {17}, pages = {4501-8}, month = {08/1997}, issn = {0270-7306}, language = {eng}, }