[Implication of integrin alpha5beta1 in human breast carcinoma apoptosis and drug resistance].

Abstract

Doxorubicin-resistant MCF-7Dox line, which is a derivative of the drug-sensitive MCF-7 human breast carcinoma line, differs from the latter by a strongly reduced expression of the alpha2beta1 integrin and a highly increased expression of the alpha5beta1 receptor. Silencing of this integrin in the MCF-7Dox cells by transfection with alpha5-specific siRNA markedly stimulated anoikis and increased sensitivity of the cells to doxorubicin. Alpha5beta1 silencing also leads to significant inhibition of the activity of kinases Akt and Erk2 in MCF-7Dox cells. Our results suggest that integrins alpha5beta1-induced signals, controlling distinct aspects of cell behavior, are conducted through the common signal pathways.

• Authors: G E Morozevich, N I Kozlova, N A Ushakova, M E Preobrazhenskaia, A E Berman
• Journal: Biomeditsinskaia khimiia (Biomed Khim) 2011 Jan-Feb Vol. 57 Issue 1 Pg. 77-84 ISSN: 2310-6972 [Print] Russia (Federation)
• PMID: 21516779 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Integrin alpha5beta1
• Neoplasm Proteins
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (pharmacokinetics)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Integrin alpha5beta1 (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Signal Transduction (drug effects, genetics)