Transcriptional expression of survivin and its splice variants in brain tumors in humans

Transcriptional expression of survivin and its splice variants in brain tumors in humans
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DOI:
10.3171/jns.2003.99.4.0738
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发表时间:
2003-10-01
影响因子:
4.1
通讯作者:
Miyatake, S
Miyatake, S
中科院分区:
医学1区
文献类型:
--
作者:
Yamada, Y;Kuroiwa, T;Miyatake, S

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Object. Survivin是一种凋亡抑制蛋白,在人类的大多数癌症中被检测到。另外,已经鉴定了两种剪接变体(存活素-2B和存活素-DeltaEx 3)。作者通过定量逆转录聚合酶链反应研究了9种肿瘤细胞系(包括神经胶质瘤)和25种脑肿瘤样本中生存素信使(m)RNA及其剪接变体的转录水平。并分析转录本表达水平与病理结果的相关性。使用对生存素及其任一剪接变体特异的引物对测量转录水平,并将其归一化为甘油醛6-磷酸脱氢酶。在测试的肿瘤细胞系中,胶质母细胞瘤细胞系显示出最高水平的存活素表达。在研究的脑肿瘤样本中,生存素优先在恶性脑肿瘤和胶质瘤中表达。Survivin-DeltaEx 3/Survivin在恶性脑肿瘤中的相对表达水平显著高于良性脑肿瘤。在恶性脑肿瘤中以生存素-DeltaEx 3的表达模式为主,在良性脑肿瘤中以生存素-2B的表达模式为主。所有脑肿瘤标本中Survivin mRNA表达与MIB-1标记指数呈显著线性相关。作者的结果表明,定量生存素及其剪接变体的水平对于预测胶质瘤的细胞生物学恶性程度是有用的,与其病理特征无关。
Object. Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-DeltaEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing quantitative reverse transcription-polymerase chain reaction. The correlation between transcript expression levels and pathological findings were also analyzed.Methods. Transcription levels were measured using primer pairs specific for survivin and either of its splice variants and were normalized to the glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested, glioblastoma cell lines showed the highest levels of survivin expression. Among brain tumor samples studied, survivin was preferentially expressed in malignant brain tumors and gliomas. The relative expression level of survivin-DeltaEx3/survivin was significantly higher in malignant than in benign brain tumor samples. Expression patterns were dominant for survivin-DeltaEx3 in malignant brain tumors and dominant for survivin-2B in benign ones. A significant linear correlation between survivin mRNA expression and MIB-1 labeling index was demonstrated in all brain tumor samples.Conclusions. The authors' results indicate that quantifying the levels of survivin and its splice variants is useful for the prediction of the cell biological malignancy of gliomas, independent of their pathological features.