Overexpression of cell surface cytokeratin 8 in multidrug-resistant MCF-7/MX cells enhances cell adhesion to the extracellular matrix.
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Accumulating evidence suggests that multiple complex mechanisms may be involved, simultaneously or complementarily, in the emergence and development of multidrug resistance (MDR) in various cancers. Cell adhesion-mediated MDR is one such mechanism. In the present study, we initially observed increased cell adhesion to extracellular matrix proteins by the MDR human breast tumor cell line MCF-7/MX compared to its parental cells. We then used a strategy that combined antibody-based screening technique and mass spectrometry-based proteomics to identify membrane proteins that contribute to the enhanced adhesion of MCF-7/MX cells. Using MCF-7/MX cells as immunogen, we isolated a mouse monoclonal antibody, 9C6, that preferentially reacts with MCF-7/MX cells over the parental MCF-7 cells. The molecular target of 9C6 was identified as cytokeratin 8 (CK8), which was found to be overexpressed on the cell surface of MCF-7/MX cells. We further observed that down-regulation of cell surface levels of CK8 through siRNA transfection significantly inhibited MCF-7/MX cell adhesion to fibronectin and vitronectin. In addition, anti-CK8 siRNA partially reversed the MDR phenotype of MCF-7/MX cells. Taken together, our results suggest that alterations in the expression level and cellular localization of CK8 may play a significant role in enhancing the cellular adhesion of MDR MCF-7/MX cells. (+info)
Hepatocarcinogenic susceptibility of fenofibrate and its possible mechanism of carcinogenicity in a two-stage hepatocarcinogenesis model of rasH2 mice.
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Relevance of the immunohistochemical expression of cytokeratin 8/18 for the diagnosis and classification of breast cancer.
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PURPOSE: The aim of our study was to characterize and describe the different immunohistochemical expression patterns of cytokeratin 8/18 (CK8/18) in breast tumors and to make a correlation between histopathology, immunohistochemistry for CK8/18 and its possible diagnostic value of this pair of keratins for molecular classification of breast cancers. MATERIAL AND METHODS: Forty cases of breast tumors immunostained with monoclonal antibodies against CK8/18 using a polymer based detection system and diaminobenzidine as chromogen were microscopically evaluated in normal and tumor breast tissue concerning the intensity, distribution and density of positive cells. Association with histopathology and nuclear grade were also studied. RESULTS: Three different models of positive reaction were found: (1) normal cytoplasmic with intense and diffuse pattern, (2) aberrant membrane pattern and (3) aberrant cytoplasmic granular pattern associated with membranous positive reaction. Normal expression of CK8/18 was found in 23 cases of breast cancer, aberrant membranous in nine cases and aberrant with granular pattern in four cases. Further studies will be needed to elucidate these differences and possible correlation with other molecular markers. (+info)
Insights into the mechanical properties of epithelial cells: the effects of shear stress on the assembly and remodeling of keratin intermediate filaments.
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