Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer.
Survivin is considered to be associated with tumorigenesis by regulating apoptosis and cell proliferation. Recent experimental studies reported survivin gene expression to be negatively regulated by wild-type p53. We investigated resected tumor specimens from 140 non-small cell lung cancer (NSCLC) patients. Quantitative reverse-transcription PCR analysis was performed to evaluate survivin gene expression. PCR-single strand conformation polymorphism following sequencing was performed to investigate mutations of p53. The apoptotic index and the Ki-67 proliferation index were also evaluated according to the survivin expression. The survivin expression was low in normal lung tissue. In contrast, the survivin expression varied greatly among tumor tissues. The survivin expression in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P=0.0109). The survivin expression in moderately or poorly differentiated tumors was significantly higher than that in well-differentiated tumors (P=0.0334). Furthermore, the survivin expression in tumors with mutant p53 was significantly higher than that in tumors with wild-type p53 (P=0.0026). In addition, the apoptotic index was significantly lower in high-survivin tumors than in low-survivin tumors (P<0.0001). The Ki-67 proliferation index was significantly higher in high-survivin tumors than in low-survivin tumors (P<0.0047). This study indicated survivin gene expression to be negatively regulated by p53 in NSCLC, and that survivin expression could inhibit apoptosis and accelerate tumor cell proliferation to produce more aggressive carcinomas.
Nakano
Jun
J
Second Department of Surgery, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa 761-0793, Japan.
Huang
Cheng-Long
CL
Liu
Dage
D
Ueno
Masaki
M
Sumitomo
Shinichi
S
Yokomise
Hiroyasu
H
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53