CYTOSKELETON ALTERATION IN MCF7R CELLS, A MULTIDRUG-RESISTANT HUMAN BREAST-CANCER CELL-LINE

Various cytoskeleton modifications are associated with malignant cell transformation and have been used as prognostic factors. A human breas t cancer cell line (MCF7S) and its multidrug resistant (MDR) subline ( MCF7R) were characterized here for their intermediate filaments (IFs) expression (cytokeratin 8, 18, 19 and vimentin) as a function of their resistance phenotype. Modifications of these cytoskeleton molecules w ere analyzed by flow cytometry, immunofluorescence, electrophoresis an d immunoblotting techniques. Cytokeratins 8 and 18 were similarly expr essed in the cell lines. Cytokeratin 19 was expressed in the MCF7S cel l line and not in the MCF7R variant while vimentin was highly expresse d in MCF7R and slightly in MCF7S. Analysis of Ifs after the addition o f doxorubicin (Dox) in the culture medium of MCF7S, showed an increase in cytokeratin 8 filaments. Vimentin expression in MCF7R was not modi fied in the presence of these different MDR modulators. Acquisition of MDR was associated with an increase and a redistribution of vimentin filaments characterized by a perinuclear polarization. These drug resi stance associated changes might derive from different biological proce sses triggered by chemotherapy. In conclusion, this suggests that this intermediate filament could be a marker associated with chemoresistan ce or a marker of malignancy in certain epithelial cancers.