Expression and relationship between topoisomerase I and II alpha genes in tumor and normal tissues in esophageal, gastric and colon cancers.
DNA topoisomerases are known to be nuclear enzymes that are important targets of topoisomerase I (topo I) and topoisomerase II (topo II) inhibitors in cancer chemotherapy. We investigated the mRNA expression of topo I and topo II alpha genes as assessed by northern blot analysis in tumor and the adjacent normal tissues of esophageal, gastric and colon cancers. The surgical specimens consisted of 18 tumor tissues and the adjacent normal tissues including 6 esophageal cancers, 6 gastric cancers and 6 colon cancers. We found that the mRNA expression of topo I gene was not significantly different between tumor and normal tissues in 18 surgical specimens, whereas the mRNA expression of topo II alpha gene in the all types of tumors was significantly higher than that of the adjacent normal tissues. Furthermore, the mRNA expression of topo II alpha gene in tumor and adjacent normal tissues was correlated with the S-phase population in cell cycle. Of great importance was the significant relationship between mRNA expression of topo I and topo II alpha genes in tumor and normal tissues was found in esophageal and colon cancers (p < 0.05), except in gastric cancers. These results indicate that the rationale in tumor specific chemotherapy with topo II inhibitors was based on the finding of its higher expression of topo II alpha gene in tumors than that of normal tissues, an important target of topo II inhibitors, and suggest that the sequential chemotherapy targeting topo I and topo II enzymes by modulating topo II alpha expression by topo I inhibitors might be more effective in esophageal and colon cancers, in terms of their relationship between topo I and topo II alpha expression in tumor cells.
Kim
R
R
Department of Surgical Oncology, Hiroshima University, Japan.
Ohi
Y
Y
Inoue
H
H
Toge
T
T
D000951:Antigens, Neoplasm; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004947:Esophagus / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016196:S Phase; D013270:Stomach / Q000201:enzymology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II