Drug-resistance gene expression and progression of astrocytic tumors.
To clarify the influence of biochemotherapy on the progression of astrocytic tumors, the expression of O6-methylguanine DNA-methyltransferase (MGMT) mRNA, as well as of other drug-resistance- and drug-sensitivity-related genes such as multidrug resistance gene 1, multidrug resistance-associated protein, glutathione S-transferase-pi, DNA topoisomerase II, and interferon receptor mRNA, and the interferon regulatory factor (IRF)-1 and -2 ratios in gliomas were investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean MGMT/beta2-microglobulin (beta2-MG) ratio for 130 neuroepithelial tumors was 8.2 +/- 17.8. The mean ratio of 45 glioblastomas was significantly higher than that for the other 85 tumors. In contrast, the mean of 26 low-grade gliomas was significantly lower than that of other tumors. The mean IRF-1/IRF-2 ratio of 16 other brain tumors that mainly consisted of medulloblastomas was significantly greater than that of the other 114 tumors. Almost no significant differences were observed between primary and recurrent tumors in the expression of any gene, and before and after therapy with corresponding drugs. The mean MGMT/beta2-MG ratio in primary glioblastomas was significantly higher than that in secondary tumors. These findings suggest that native drug resistance is more important than acquired resistance when glioma therapy is considered.
Tanaka
S
S
Department of Neurosurgery, Kitasato Institute Medical Center Hospital, Kitamoto, Saitama, Japan. tanaka-s@kitasato.or.jp
Kobayashi
I
I
Oka
H
H
Fujii
K
K
Watanabe
T
T
Nagashima
T
T
Hori
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis / Q000235:genetics; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D017471:Receptors, Interferon; D019853:O(6)-Methylguanine-DNA Methyltransferase; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II