Implication of integrin α5β1 in human breast carcinoma apoptosis and drug resistance
Author(s) -
G. E. Morozevich,
N. I. Kozlova,
Н. А. Ушакова,
M. E. Preobrazhenskaya,
A. E. Berman
Publication year - 2011
Publication title -
biomeditsinskaya khimiya
Language(s) - English
Resource type - Journals
eISSN - 2310-6972
pISSN - 2310-6905
DOI - 10.18097/pbmc20115701077
Subject(s) - integrin , doxorubicin , gene silencing , anoikis , breast carcinoma , cancer research , transfection , protein kinase b , cell culture , apoptosis , kinase , microbiology and biotechnology , focal adhesion , chemistry , biology , signal transduction , receptor , breast cancer , medicine , cancer , programmed cell death , chemotherapy , biochemistry , gene , genetics
Doxorubicin-resistant MCF-7Dox line, which is a derivative of the drug-sensitive MCF-7 human breast carcinima line, differs from the latter by a strongly reduced expression of the α2β1 integrin and a highly increased expression of the α5β1 receptor. Silencing of this integrin in the MCF-7Dox cells by transfection with α5-specific siRNA markedly stimulated anoikis and increased sensitivity of the cells to doxorubicin. α5β1 silencing also leads to significant inhibition of the activity of kinases Akt and Erk2 in MCF-7Dox cells. Our results suggest that integrins α5β1-induced signals, controlling distinct aspects of cell behavior, are conducted through the common signal pathways.
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