title: Mutation of β-catenin in a radiation and estrogen breast cancer model.
abstract: β-catenin plays a pivotal role in cell-to-cell adhesion as a transcriptional activator in signal transduction pathways. Potential role of this gene was studied in a radiation- and estrogen breast cancer model by analyzing differential expression of associated genes of β-catenin as E-cadherin and catenins. The aim was to identify whether β-catenin gene was mutated when associated with other genes as glycogen synthase kinase-3-β (GSK-3-β), T-cell factor (TCF) and other extracellular matrix genes related to cell adhesion. Results indicated that β-catenin gene had increased expression at mRNA and mutation at exon 3 in irradiated and estrogen-treated cell lines when compared to MCF-10F. It was found that β-catenin and GSK-3-β had greater protein expression in the tumorigenic cell line, called Alpha5 and the tumor cell lines, called Tumor2 than control MCF-10F and non-malignant Alpha3 cell lines. The β-catenin/GSK-3-β complex was identified in non-malignant cell lines such as MCF-10F, Estrogen, Alpha1, Alpha3, and Alpha4 cell lines by immunoprecipitation assays. However, Alpha5 and Tumor2 did not form a complex in this assay. However, β-catenin/TCF-4 complex was found only in Alpha5 and Tumor2. Immunofluorescent studies confirmed these findings since co-localization in β-catenin and GSK-3-β was only found in MCF-10F and Alpha3 while β-catenin/TCF-4 was only observed in Alpha5 and Tumor2. It can be concluded that mutation of β-catenin and its interaction with other associated proteins may be an early event during radiation and estrogen induced progression of human breast carcinogenesis.
authors.affiliation: Department of Natural Sciences, Hostos College, The City University of New York, Bronx, NY, USA.
authors.forename: Debasish
authors.initials: D
authors.lastname: Roy
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, NY, USA.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Calaf
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D018450:Disease Progression; D004967:Estrogens; D005260:Female; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D014965:X-Rays; D051176:beta Catenin / Q000235:genetics*
chemical_list: D004967:Estrogens; D051176:beta Catenin