Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 46, Issue 1, Pages 153-160Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2014.2722
Keywords
estrogen; radiation; beta-catenin; breast cancer
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Funding
- FONDECYT [1120006]
- MINEDUC-Universidad de Tarapaca, Chile
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beta-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 beta-catenin as E-cadherin and catenins. The aim was to identify whether beta-catenin gene was mutated when associated with other genes as glycogen synthase kinase-3-beta (GSK-3-beta), T-cell factor (TCF) and other extracellular matrix genes related to cell adhesion. Results indicated that beta-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 beta-catenin and GSK-3-beta 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 beta-catenin/GSK-3 beta complex was identified in non-malignant cell lines such as MCF-10F, Estrogen, Alphal, Alpha3, and Alpha4 cell lines by immunoprecipitation assays. However, Alpha5 and Tumor2 did not form a complex in this assay. However, beta-catenin/TCF-4 complex was found only in Alpha5 and Tumor2. Immunofluorescent studies confirmed these findings since co-localization in beta-catenin and GSK-3-beta was only found in MCF-10F and Alpha3 while beta-catenin/TCF-4 was only observed in Alpha5 and Tumor2. It can be concluded that mutation of beta-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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