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2016 ; 16
(ä): 236
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Snail-induced epithelial-to-mesenchymal transition of MCF-7 breast cancer cells:
systems analysis of molecular changes and their effect on radiation and drug
sensitivity
#MMPMID26988558
Mezencev R
; Matyunina LV
; Jabbari N
; McDonald JF
BMC Cancer
2016[Mar]; 16
(ä): 236
PMID26988558
show ga
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been associated with
the acquisition of metastatic potential and the resistance of cancer cells to
therapeutic treatments. MCF-7 breast cancer cells engineered to constitutively
express the zinc-finger transcriptional repressor gene Snail (MCF-7-Snail cells)
have been previously shown to display morphological and molecular changes
characteristic of EMT. We report here the results of a comprehensive systems
level molecular analysis of changes in global patterns of gene expression and
levels of glutathione and reactive oxygen species (ROS) in MCF-7-Snail cells and
the consequence of these changes on the sensitivity of cells to radiation
treatment and therapeutic drugs. METHODS: Snail-induced changes in global
patterns of gene expression were identified by microarray profiling using the
Affymetrix platform (U133 Plus 2.0). The resulting data were processed and
analyzed by a variety of system level analytical methods. Levels of ROS and
glutathione (GSH) were determined by fluorescent and luminescence assays, and
nuclear levels of NF-?B protein were determined by an ELISA based method. The
sensitivity of cells to ionizing radiation and anticancer drugs was determined
using a resazurin-based cell cytotoxicity assay. RESULTS: Constitutive ectopic
expression of Snail in epithelial-like, luminal A-type MCF-7 cells induced
significant changes in the expression of >7600 genes including gene and miRNA
regulators of EMT. Mesenchymal-like MCF-7-Snail cells acquired molecular profiles
characteristic of triple-negative, claudin-low breast cancer cells, and displayed
increased sensitivity to radiation treatment, and increased, decreased or no
change in sensitivity to a variety of anticancer drugs. Elevated ROS levels in
MCF-7-Snail cells were unexpectedly not positively correlated with NF-?B
activity. CONCLUSIONS: Ectopic expression of Snail in MCF-7 cells resulted in
morphological and molecular changes previously associated with EMT. The results
underscore the complexity and cell-type dependent nature of the EMT process and
indicate that EMT is not necessarily predictive of decreased resistance to
radiation and drug-based therapies.