Mutation of β-catenin in a radiation and estrogen breast cancer model

Roy,Debasish; Calaf,Gloria M.

doi:10.3892/ijo.2014.2722

Mutation of β-catenin in a radiation and estrogen breast cancer model

Authors:
- Debasish Roy
- Gloria M. Calaf
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Affiliations: Department of Natural Sciences, Hostos College, The City University of New York, Bronx, NY, USA, Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
Published online on: October 22, 2014 https://doi.org/10.3892/ijo.2014.2722
Pages: 153-160

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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.

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