Abstract
We studied the effect of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) on human gastric cancer cell lines. Cell proliferation in 3 of 8 cell lines was effectively inhibited by everolimus. Basal phosphorylation level of 4E-BP1 (T37/46, T70) was significantly higher in everolimus-sensitive cells than in everolimus-resistant cells. In subcutaneous xenograft model, immunohistochemistry analysis revealed that everolimus-sensitive cells expressed high levels of phospho-4E-BP1 (T37/46). In conclusion, phosphorylation of 4E-BP1 may be a predictive biomarker of everolimus sensitivity in gastric cancer.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Cycle Proteins
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Everolimus
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Flow Cytometry
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Humans
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Immunohistochemistry
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Phosphoproteins / metabolism*
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Phosphorylation
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Sirolimus / analogs & derivatives*
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Sirolimus / pharmacology
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology*
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TOR Serine-Threonine Kinases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antineoplastic Agents
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Cell Cycle Proteins
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EIF4EBP1 protein, human
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Phosphoproteins
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Everolimus
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MTOR protein, human
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TOR Serine-Threonine Kinases
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Sirolimus