© Copyright 2008 by the Society for Neuro-Oncology
Received October 3, 2007
Accepted February 11, 2008
GRP78 is overexpressed in glioblastomas and regulates glioma cell growth and apoptosis
Hae Kyung Lee 1,
Cunli Xiang 1,
Simona Cazacu 1,
Susan Finniss 1,
Gila Kazimirsky 1,
Nancy Lemke 1,
Norman L. Lehman 1,
Sandra A. Rempel 1,
Tom Mikkelsen 1,
Chaya Brodie 1*
1 Department of Neurosurgery and Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA
* To whom correspondence should be addressed. E-mail: nscha{at}neuro.hfh.edu.
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Abstract |
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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 
-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.
Key Words:
apoptosis, caspase 7, glioblastoma, GRP78, survival
