Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression.
Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression.
复制标题
胃癌中不同生存变异的表达：源于苏属-2b在肿瘤进展中的作用的第一线索。
DOI：
10.1038/sj.bjc.6600153
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发表时间：
2002-03-04
影响因子：
8.8
通讯作者：
Gerharz, C D
中科院分区：
文献类型：
--
作者：
Krieg, A;Mahotka, C;Krieg, T;Grabsch, H;Muller, W;Takeno, S;Suschek, C V;Heydthausen, M;Gabbert, H E;Gerharz, C D
Survivin是细胞凋亡抑制因子家族的新成员，它决定了肿瘤细胞对促凋亡刺激的敏感性。最近，我们发现了两个新的Survivin剪接变异体，它们具有不同的抗凋亡特性：Survivin-ΔEX3的抗凋亡能力被保留，而Survivin-2B失去了抗凋亡能力，可能是Survivin的天然拮抗剂。由于到目前为止还没有发现这些选择性剪接变异体在体内的表达，所以我们分析了不同组织学亚型、分级和分期的胃癌。由于目前还没有抗体可用于确定新的剪接变体，因此使用从30种不同胃癌获得的RNA样本进行了定量逆转录聚合酶链式反应。聚合酶链式反应产物用密度计量学方法进行定量。我们发现，所有的胃癌，无论其组织类型、分级或分期，都表达Survivin-ΔEX3、Survivin-2B和Survivin，后者是主要的转录本。I+II期与III+IV期比较，Survivin和Survivin-ΔEx3的表达无明显变化。相反，Survivin-2B的表达呈明显的分期依赖性下降(P=0.033)。我们的研究首次证明了不同剪接变异体在胃癌中的表达，并为Survivin-2B在肿瘤进展中的作用提供了第一条线索。《英国癌症杂志》(2002)86,737-743。DOI：10.1038/sj/bjc/6600153 www.bjancer.com2002英国癌症研究中心
Survivin is a novel member of the inhibitor of apoptosis family and determines the susceptibility of tumour cells to pro-apoptotic stimuli. Recently, we identified two novel alternative splice variants of survivin, differing in their anti-apoptotic properties: whereas the anti-apoptotic potential of survivin-ΔEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin. Because the in vivo expression of these alternative splice variants has not been explored so far, we analysed gastric carcinomas of different histological subtypes, grades and stages. Since no antibodies are currently available to determine the novel splice variants, quantitative reverse transcriptase polymerase chain reaction was performed, using RNA samples obtained from 30 different gastric carcinomas. Polymerase chain reactions products were quantified by densitometric evaluation. We found that all gastric carcinomas, irrespective of their histological types, grades or stages, express survivin-ΔEx3, survivin-2B and survivin, the latter being the dominant transcript. Comparing the disease stages I+II with III+IV, expression of survivin and survivin-ΔEx3 remained unchanged. In contrast, a significant (P=0.033) stage-dependent decrease in the expression of survivin-2B became evident. Our study demonstrates for the first time the expression of alternative splice variants in gastric carcinomas and provides a first clue to a role of survivin-2B in tumour progression. British Journal of Cancer (2002) 86, 737–743. DOI: 10.1038/sj/bjc/6600153 www.bjcancer.com © 2002 Cancer Research UK