Portal de Periódicos da CAPES

HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations

2015; Springer Science+Business Media; Volume: 32; Issue: 2 Linguagem: Inglês

10.1007/s10585-015-9694-5

1573-7276

F. Darío Cuello-Carrión, Jorge Eduardo Shortrede, Daiana Alvarez-Olmedo, Niubys Cayado-Gutiérrez, Gisela N. Castro, Felipe Carlos Martín Zoppino, Martín Guerrero, Estefanía M. Martinis, Rodolfo G. Wuilloud, Nidia N. Gómez, Verónica S. Biaggio, Javier I. J. Orozco, Francisco E. Gago, Leonardo Andrés Ciocca, Mariel A. Fanelli, Daniel R. Ciocca,

Cancer Cells and Metastasis

In human breast cancer, β-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 β-catenin/HER2 has been reported, in the present study we have explored whether β-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 β-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 co-expression of β-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 β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-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 β-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 β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.