Mutation of the p53 gene in human astrocytic tumours correlates with increased resistance to DNA-damaging agents but not to anti-microtubule anti-cancer agents.
Astrocytic tumours often become resistant to a variety of chemotherapeutic agents in advanced stages and frequently possess mutations in the p53 tumour-suppressor gene. Previous studies using established cell lines to investigate the relation between mutated p53 genes and altered resistance to anti-cancer agents brought inconsistent results. In this report, we examined the status of the p53 gene in 56 astrocytic tumour specimens by single-strand conformation polymorphism and their in vitro chemosensitivity to 30 different kinds of anti-cancer agents. The chemosensitivity was determined by drug-induced cell death using flow cytometry. We found that the mutated p53 gene correlated with increased resistance to DNA-damaging agents but the sensitivity to anti-microtubule agents was independent of the mutation, suggesting a clinical significance of the status of p53 gene in astrocytic tumours and a rational application of anti-microtubule agents to the patients with p53-mutated astrocytic tumours.
Iwadate
Y
Y
Department of Neurosurgery, School of Medicine, Chiba University, Japan.
Tagawa
M
M
Fujimoto
S
S
Hirose
M
M
Namba
H
H
Sueyoshi
K
K
Sakiyama
S
S
Yamaura
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004273:DNA, Neoplasm / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm