A study of the expression of four chemoresistance-related genes in human primary and metastatic brain tumours.
We investigated four mechanisms of intrinsic chemoresistance in a series of 67 human brain tumours including 31 gliomas (one grade I ganglioglioma, nine grade II and 10 grade III astrocytomas, 11 glioblastomas), 13 cerebral metastases, one medulloblastoma, one malignant teratoma, three ependymomas and 18 meningiomas. We studied four genes by northern blotting: multidrug-resistance (MDR 1), glutathione-s transferase (GST pi), dihydrofolate reductase (DHFR), and topoisomerase II (Topo II). The Topo II gene was absent in the normal adult brain (100%) and in 64% of the tumour samples tested. A second gene, GST pi, was found to be overexpressed in 38% of brain tumours. The two other chemoresistance-related genes were occasionally overexpressed in brain tumours (2% for MDR1, 9% for DHFR). Our results provide evidence that chemoresistance is intrinsic to the brain tissue and seems likely to be a multifactorial process.
Unité d'Oncologie Médicale, C.H.U.R.G., Grenoble, France.
M
M
Mousseau
C
C
Chauvin
M F
MF
Nissou
M
M
Chaffanet
D
D
Plantaz
B
B
Pasquier
R
R
Schaerer
A
A
Benabid
D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013762:Tetrahydrofolate Dehydrogenase; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II