Survivin promotes cell proliferation in human hepatocellular carcinoma
Survivin promotes cell proliferation in human hepatocellular carcinoma
复制标题
DOI：
10.1053/he.2000.6496
复制
发表时间：
2000-05-01
期刊：
影响因子：
13.5
通讯作者：
Suzuki, A
中科院分区：
文献类型：
--
作者：
Ito, T;Shiraki, K;Suzuki, A
Survivin是一种新近发现的凋亡抑制因子。由于细胞凋亡的抑制是重要的癌变和肿瘤生长，我们研究了生存素在人肝细胞癌（HCC）的表达和功能。我们已经表明，4肝癌细胞系和7 8人肝癌组织表达生存素信使RNA（mRNA），而生存素mRNA的表达在正常肝脏和非肿瘤区域的这些组织中使用逆转录聚合酶链反应检测不到。免疫荧光染色显示Survivin主要分布于细胞核内。此外，20例HCC组织中有14例（70%）显示Survivin核染色阳性，而非肿瘤组织的免疫组化染色很少。Survivin的表达与肝癌组织的增殖指数密切相关，而与凋亡指数无明显相关性。因此，我们在转染survivin后进行细胞周期分析，结果显示survivin过表达导致所有4个HCC细胞系的G（0）/G（1）期减少和S期增加。此外，我们还发现Survivin与细胞周期蛋白依赖性激酶4（Cdk 4）相互作用，并通过过度表达Survivin从Cdk 4中释放p21（WAF 1/Cip 1）（p21），由此我们得出结论：Survivin通过与Cdk 4相互作用并从Cdk 4中释放p21来促进细胞增殖。这可能在人类HCC的发生和发展中起重要作用。
Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4, From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.