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 breast 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 were analyzed by flow cytometry, immunofluorescence, electrophoresis and immunoblotting techniques. Cytokeratins 8 and 18 were similarly expressed in the cell lines. Cytokeratin 19 was expressed in the MCF7S cell line and not in the MCF7R variant, while vimentin was highly expressed in MCF7R and slightly in MCF7S. Analysis of IFs after the addition of doxorubicin (Dox) in the culture medium of MCF7S, showed an increase in cytokeratin 8 filaments. Vimentin expression in MCF7R was not modified 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 resistance associated changes might derive from different biological processes triggered by chemotherapy. In conclusion, this suggests that this intermediate filament could be a marker associated with chemoresistance or a marker of malignancy in certain epithelial cancers.
Bichat
F
F
Medical Oncology Department, Pitié-Salpetriere Hospital, Paris, France.
Mouawad
R
R
Solis-Recendez
G
G
Khayat
D
D
Bastian
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000648:ultrastructure*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D007633:Keratins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014746:Vimentin; D007633:Keratins; D004317:Doxorubicin