EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer
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Maria J. Serrano1,2,*, Francisco G. Ortega1,*, Maria J. Alvarez-Cubero1,2, Rosa Nadal3, Pedro Sanchez-Rovira4, Marta Salido5, María Rodríguez5, Jose L. García-Puche1, Miguel Delgado-Rodriguez4, Francisco Solé6,7, Maria A. García8, Macarena Perán4,10, Rafael Rosell9, Juan A. Marchal10,11 and Jose A. Lorente1,2
1 GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain
2 Laboratory of Genetic Identification-UGR, Department of Legal Medicine, University of Granada, Granada, Spain
3 Hospital de Barcelona, Medical Oncology Department, Barcelona, Spain
4 University of Jaén, Division of Preventive Medicine and Public Health, CIBERESP, Jaén, Spain
5 Molecular Cytogenetics Laboratory; Pathology Department, Parc de Salut Mar-Hospital del Mar-IMIM-GRETNHE, Barcelona, Spain
6 Medicine Department. Universitat Autònoma de Barcelona, Barcelona, Spain
7 Institut de Recerca contra la Leucèmia Josep Carreras, Badalona, Spain
8 Department of Oncology, Virgen de las Nieves, University Hospital, Granada, Spain
9 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain (RR); Pangaea Biotech SL, USP Dexeus University Institute, Barcelona, Spain (RR, MAM)
10 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain
11 Department of Human Anatomy and Embryology, University of Granada, Granada, Spain
* These authors contributed equally to this work
Jose A Lorente, email:
Juan Antonio Marchal, email:
Keywords: Breast Cancer, Circulating Tumor Cells, EGFR, Epithelial-Mesenchymal Transition, Vimentin, Slug, Bcl-2, Apoptosis
Received: May 16, 2014 Accepted: July 13, 2014 Published: July 14, 2014
Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.
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