Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer.
Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer.
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DOI：
10.3892/ijo.27.5.1215
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发表时间：
2005-11
影响因子：
5.2
通讯作者：
J. Nakano;Cheng‐long Huang;Dage Liu;M. Ueno;S. Sumitomo;H. Yokomise
中科院分区：
文献类型：
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作者：
J. Nakano;Cheng‐long Huang;Dage Liu;M. Ueno;S. Sumitomo;H. Yokomise
Survivin被认为通过调节细胞凋亡和细胞增殖与肿瘤发生有关。最近的实验研究报道生存素基因表达受野生型p53负调控。我们研究了140例非小细胞肺癌（NSCLC）患者的切除肿瘤标本。定量逆转录PCR分析进行评估生存素基因的表达。PCR-单链构象多态性测序后进行调查的p53突变。以Survivin的表达为指标，计算细胞凋亡指数和Ki-67增殖指数。Survivin在正常肺组织中呈低表达。相反，Survivin在肿瘤组织中的表达差异很大。Survivin在鳞癌中的表达显著高于腺癌（P=0.0109）。Survivin在中、低分化肿瘤中的表达明显高于高分化肿瘤（P=0.0334）。突变型p53肿瘤中survivin的表达显著高于野生型p53肿瘤（P=0.0026）。此外，高生存素肿瘤的凋亡指数显著低于低生存素肿瘤（P<0.0001）。高Survivin表达组Ki-67增殖指数明显高于低Survivin表达组（P<0.0047）。本研究表明，在NSCLC中，survivin基因表达受p53负调控，survivin表达可抑制细胞凋亡，促进肿瘤细胞增殖，从而产生更具侵袭性的肿瘤。
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.