Overexpression of the human major vault protein in astrocytic brain tumor cells.
Evidence has shown that the major human vault protein (MVP), which is identical to lung resistance-related protein (LRP), may be causally involved in a special type of multidrug resistance (MDR). The purpose of this study was to investigate the expression and cellular localization of MVP in cells derived from brain tumors and other tumors of neuroectodermal origin. Using both established cell lines (n = 22) and primary explants (n = 30), we show that a distinct overexpression of the MVP gene at the mRNA (RT-PCR) and protein (Western blot) levels is a characteristic feature of cells derived from astrocytic brain tumors. Primary cultures obtained from meningioma specimens also expressed high MVP levels, in contrast to neuroblastoma and medulloblastoma cells, which rarely contained detectable amounts of MVP. Normal human astrocytes cultured in vitro expressed MVP, although at low amounts compared with most malignant cell types. Basal MVP expression correlated with resistance against diverse antineoplastic drugs including anthracyclins, cisplatin and etoposide. By Western blot, MVP was also detected in all tumor samples taken from 7 glioma and 3 meningioma patients. Taken together, these data suggest overexpression of MVP as one explanation for the low efficacy of chemotherapeutic treatment of astrocytic brain tumors.
Berger
W
W
Institute of Cancer Research, Division of Applied and Experimental Oncology, Borschke gasse 8a Vienna University, Vienna, Austria. walter.berger@univie.ac.at
Spiegl-Kreinecker
S
S
Buchroithner
J
J
Elbling
L
L
Pirker
C
C
Fischer
J
J
Micksche
M
M
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015151:Immunoblotting; D008579:Meningioma / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein