title: HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations.
abstract: 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.
authors: Laboratory of Oncology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Technology and Scientific Center (CCT)-National Research Council of Argentina (CONICET), Ruiz Leal s/n, Parque General San Martín, 5500, Mendoza, Argentina, dcuello@mendoza-conicet.gob.ar.
authors: F Darío
authors: FD
authors: Cuello-Carrión
authors: Jorge E
authors: JE
authors: Shortrede
authors: Daiana
authors: D
authors: Alvarez-Olmedo
authors: Niubys
authors: N
authors: Cayado-Gutiérrez
authors: Gisela N
authors: GN
authors: Castro
authors: Felipe C M
authors: FC
authors: Zoppino
authors: Martín
authors: M
authors: Guerrero
authors: Estefania
authors: E
authors: Martinis
authors: Rodolfo
authors: R
authors: Wuilloud
authors: Nidia N
authors: NN
authors: Gómez
authors: Verónica
authors: V
authors: Biaggio
authors: Javier
authors: J
authors: Orozco
authors: Francisco E
authors: FE
authors: Gago
authors: Leonardo A
authors: LA
authors: Ciocca
authors: Mariel A
authors: MA
authors: Fanelli
authors: Daniel R
authors: DR
authors: Ciocca
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D002104:Cadmium / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007150:Immunohistochemistry; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D016896:Treatment Outcome; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002104:Cadmium; D006861:Hydrogen Peroxide; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D051176:beta Catenin; C495270:CTNNB1 protein, human; C508053:ERBB2 protein, human
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