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The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays
Ist Teil von
Molecular cancer therapeutics, 2006-08, Vol.5 (8), p.2115-2120
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2006
Quelle
MEDLINE
Beschreibungen/Notizen
Doxorubicin is considered to be the most effective agent in the treatment of breast cancer patients. Unfortunately, resistance
to this agent is common, representing a major obstacle to successful treatment. The identification of novel biomarkers that
are able to predict treatment response may allow therapy to be tailored to individual patients. Antibody microarrays provide
a powerful new technique, enabling the global comparative analysis of many proteins simultaneously. This technology may identify
a panel of proteins to discriminate between drug-resistant and drug-sensitive samples. The Panorama Cell Signaling Antibody
Microarray was exploited to analyze the MDA-MB-231 breast cancer cell line and a novel derivative, which displays significant
resistance to doxorubicin at clinically relevant concentrations. The microarray comprised 224 antibodies selected from a variety
of pathways, including apoptotic and cell signaling pathways. A standard ≥2.0-fold cutoff value was used to determine differentially
expressed proteins. A decrease in the expression of mitogen-activated protein kinase–activated monophosphotyrosine (phosphorylated
extracellular signal-regulated kinase; 2.8-fold decrease), cyclin D2 (2.5-fold decrease), cytokeratin 18 (2.5-fold decrease),
cyclin B1 (2.4-fold decrease), and heterogeneous nuclear ribonucleoprotein m3-m4 (2.0-fold decrease) was associated with doxorubicin
resistance. Western blotting was exploited to confirm results from the antibody microarray experiment. These results suggest
that antibody microarrays can be used to identify novel biomarkers and further validation may reveal mechanisms of chemotherapy
resistance and identify potential therapeutic targets. [Mol Cancer Ther 2006;5(8):2115–20]