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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness.
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Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness.

机译：Seladin-1和睾丸生殖细胞肿瘤：对顺铂反应性的新见解。

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The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis. The aim of our study was to assess the expression of seladin-1 in different histological types of TGCTs, known to have varying treatment sensitivity, in order to establish whether this protein may influence cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA and at the protein level, were higher in the adjacent normal parenchyma than in the pathological counterparts. In tumoural tissues, the level of expression differed among TGCT histological types. The highest tumour-expression level was found in teratoma, whereas the lowest was detected in seminoma, corresponding to the different chemo/and radiosensitivities of these tumour types. In common with other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic properties through inhibition of caspase-3 activation. We confirmed our results using a non-seminomatous cell line model (NT2) before and after differentiation with retinoic acid. Significantly higher seladin-1 expression was observed in the differentiated derivatives (teratoma) and an inverse relationship was found between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1 silencing or overexpression in this cell line supports involvement of seladin-1 in cisplatin responsiveness. Seladin-1 silencing was associated with greater cisplatin responsiveness demonstrated by decreased cell viability and increased expression of apoptotic markers. In contrast, overexpression of seladin-1 was associated with a higher survival rate and a clear anti-apoptotic effect. In conclusion, we have demonstrated for the first time an important role for seladin-1 in the biology of TGCTs and provided new insights into cisplatin responsiveness of these tumours.
机译：到目前为止，尚未完全阐明青少年和成人睾丸生殖细胞肿瘤（TGCT）（即精原细胞瘤和非精原细胞生殖细胞肿瘤）对化学/放射疗法的敏感性的分子基础。已经提出，它可能取决于细胞凋亡调控中涉及的因素。 Seladin-1是一种涉及多种生物过程（包括细胞凋亡）的多功能蛋白。我们研究的目的是评估seladin-1在不同组织学类型TGCT（已知具有不同的治疗敏感性）中的表达，以确定该蛋白是否可能在体外影响顺铂反应性。在邻近的正常实质中，在mRNA和蛋白质水平上的Seladin-1表达水平均高于病理对应物。在肿瘤组织中，TGCT组织学类型的表达水平不同。在畸胎瘤中发现最高的肿瘤表达水平，而在精原细胞中发现最低的肿瘤表达水平，这对应于这些肿瘤类型的不同化学/放射敏感性。与其他癌症一样，在TGCT衍生的细胞系中，Seladin-1通过抑制caspase-3活化而显示出抗凋亡特性。我们用视黄酸分化前后使用非亚细胞瘤细胞系模型（NT2）确认了我们的结果。在分化的衍生物（畸胎瘤）中观察到seladin-1表达显着较高，并且在seladin-1表达与裂解的caspase-3的量之间发现反比关系。 Seladin-1沉默或在该细胞系中的过度表达支持seladin-1参与顺铂反应。 Seladin-1沉默与更高的顺铂反应性相关，这表现为细胞活力降低和凋亡标记物表达增加。相反，seladin-1的过表达与更高的生存率和明显的抗凋亡作用有关。总之，我们首次证明了seladin-1在TGCT生物学中的重要作用，并提供了对这些肿瘤的顺铂反应性的新见解。

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