Abstract
We characterized the expression and function of the endoplasmic reticulum protein GRP78 in glial tumors. GRP78 is highly expressed in glioblastomas but not in oligodendrogliomas, and its expression is inversely correlated with median patient survival. Overexpression of GRP78 in glioma cells decreases caspase 7 activation and renders the cells resistant to etoposide- and cisplatin-induced apoptosis, whereas silencing of GRP78 decreases cell growth and sensitizes glioma cells to etoposide, cisplatin, and gamma-radiation. Thus, GRP78 contributes to the increased apoptosis resistance and growth of glioma cells and may provide a target for enhancing the therapeutic responsiveness of these tumors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology*
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Biomarkers, Tumor / analysis
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Blotting, Western
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Brain Neoplasms / metabolism*
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Brain Neoplasms / mortality
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Caspase 7
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Cell Line, Tumor
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Cell Proliferation*
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Drug Resistance, Neoplasm / physiology
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Endoplasmic Reticulum Chaperone BiP
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Enzyme Activation / physiology
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Gene Expression
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Gene Expression Profiling
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Glioma / metabolism*
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Glioma / mortality
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Heat-Shock Proteins / biosynthesis*
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Humans
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Immunohistochemistry
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Molecular Chaperones / biosynthesis*
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Oligonucleotide Array Sequence Analysis
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
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Up-Regulation
Substances
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Biomarkers, Tumor
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Endoplasmic Reticulum Chaperone BiP
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HSPA5 protein, human
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Heat-Shock Proteins
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Molecular Chaperones
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Caspase 7