GRP78 is overexpressed in glioblastomas and regulates glioma cell growth and apoptosis.
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.
Lee
Hae Kyung
HK
Department of Neurosurgery and Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA.
Xiang
Cunli
C
Cazacu
Simona
S
Finniss
Susan
S
Kazimirsky
Gila
G
Lemke
Nancy
N
Lehman
Norman L
NL
Rempel
Sandra A
SA
Mikkelsen
Tom
T
Brodie
Chaya
C
D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D053179:Caspase 7; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling; D005910:Glioma / Q000378:metabolism* / Q000401:mortality; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D053179:Caspase 7