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Survivin 在小儿霍奇金淋巴瘤肿瘤细胞中的过表达:蛋白表达及剪接变异转录谱的特征。

Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile.

机构信息

Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.

Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.

出版信息

Exp Mol Pathol. 2019 Jun;108:24-31. doi: 10.1016/j.yexmp.2019.03.005. Epub 2019 Mar 12.

DOI:10.1016/j.yexmp.2019.03.005
PMID:30876863
Abstract

Survivin is abundantly expressed during fetal development but absent in most differentiated adult tissues; an exception being components of the immune system, such as B and T lymphocytes. Beyond acting as a master regulator of the cell cycle, survivin acts as an inhibitor of apoptosis and is overexpressed in almost all carcinoma types; however, its expression in lymphomas is lesser-explored. Survivin's role in carcinogenesis was subjected to its sub-cellular localization and splice transcripts expression, namely wild-type survivin, survivin-∆Ex3 and survivin-2B. To assess survivin's expression and sub-cellular localization in Epstein Barr virus positive and negative biopsies from treatment naïve pediatric patients with Hodgkin lymphoma (HL), samples were stained for survivin protein by immunofluorescence. The proportion of survivin+ cells was calculated, survivin sub-cellular localization assessed and its fluorescence intensity quantified. Transcription profile of survivin mRNA variants was studied by RT-qPCR. Survivin was overexpressed in the nucleus of tumor cells, and also in a greater proportion of tumor cells, in comparison with the non-tumoral infiltrating cells. Although a higher expression of survivin was observed in advanced clinical stages, no correlation was found between the expression level of survivin and a proliferation marker, or event-free survival. Instead, survivin was related to apoptosis inhibition in tumor cells. Additionally, survivin's transcriptional variants displayed similar expression levels. Present results suggest that although survivin is overexpressed in Hodgkin's tumor cells, it may not play a central role in the progression of classic HL, or act as a suitable progression biomarker, as suggested for most carcinomas.

摘要

生存素在胎儿发育过程中大量表达,但在大多数分化的成人组织中不存在;免疫细胞如 B 和 T 淋巴细胞是个例外。生存素不仅作为细胞周期的主要调节因子,还作为凋亡抑制剂,在几乎所有癌类型中均过度表达;然而,其在淋巴瘤中的表达尚未得到充分探索。生存素在癌变中的作用与其亚细胞定位和剪接转录本表达有关,即野生型生存素、生存素-∆Ex3 和生存素-2B。为了评估 EBV 阳性和阴性的初治儿童霍奇金淋巴瘤(HL)患者活检组织中生存素的表达和亚细胞定位,我们通过免疫荧光法对生存素蛋白进行染色。计算了生存素+细胞的比例,评估了生存素的亚细胞定位,并对其荧光强度进行了定量。通过 RT-qPCR 研究了生存素 mRNA 变体的转录谱。与非肿瘤浸润细胞相比,在肿瘤细胞的细胞核中以及在更大比例的肿瘤细胞中,生存素过表达。尽管在较晚期的临床分期中观察到生存素的表达较高,但未发现生存素的表达水平与增殖标志物或无事件生存之间存在相关性。相反,生存素与肿瘤细胞的凋亡抑制有关。此外,生存素的转录变体表达水平相似。本研究结果表明,尽管生存素在霍奇金肿瘤细胞中过度表达,但它可能在经典 HL 的进展中不起核心作用,也不能像大多数癌中那样作为合适的进展生物标志物。

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Exp Mol Pathol. 2019 Jun;108:24-31. doi: 10.1016/j.yexmp.2019.03.005. Epub 2019 Mar 12.
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