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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Liu
Dage
D
Second Department of Surgery, Kagawa Medical University, Kagawa, Japan.
Huang
Cheng-long
CL
Kameyama
Kotaro
K
Hayashi
Eiichi
E
Yamauchi
Akira
A
Sumitomo
Shinichi
S
Yokomise
Hiroyasu
H
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D017931:DNA Primers; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000951:Antigens, Neoplasm; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II