Topoisomerase IIalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.

Abstract

Topoisomerase IIalpha (Topo IIalpha) is an essential nuclear enzyme for chromosome segregation during mitosis. Previous experimental studies using cell lines reported that Topo IIalpha expression was negatively regulated by wild-type p53 through the gene's promoter region. Surgically resected tumor specimens from 98 nonsmall cell lung carcinoma (NSCLC) patients who were not treated with preoperative chemotherapy were studied. Quantitative reverse-transcription polymerase chain reaction analysis was done to evaluate Topo IIalpha gene expression. Polymerase chain reaction single strand conformation polymorphism following sequencing was performed to investigate mutations of p53. Topo IIalpha gene expression in squamous cell carcinomas was significantly higher than in adenocarcinomas (P = 0.0007). Topo IIalpha gene expression in moderately differentiated tumors and poorly differentiated tumors was significantly higher than in well differentiated tumors (P = 0.0032 and P = 0.0005, respectively). Thirty nine tumors (40%) had mutations of p53. Topo IIalpha gene expression in tumors with mutant p53 was significantly higher than in those with wild-type p53 (P = 0.0224). The current study suggests that Topo IIalpha gene expression is regulated by p53 gene status in NSCLC patients and that the overexpression of Topo IIalpha induced by mutant p53 might cause more aggressive carcinogenesis.