Daniel R Ciocca
National Research Council of Argentina, Argentina
Posters-Accepted Abstracts: J Cancer Sci Ther
In human breast cancer, �²-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup and that in breast cancer cells a direct interaction of �²-catenin/HER2 has been reported, in the present study we have explored whether �²-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n=140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed �²-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the coexpression of �²-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different �²-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in �²-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and �²-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated �²-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.
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