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一组伊朗乳腺癌患者中半胱天冬酶8的下调——一项初步研究。

Downregulation of Caspase 8 in a group of Iranian breast cancer patients - A pilot study.

作者信息

Aghababazadeh Masoumeh, Dorraki Najmeh, Javan Fahimeh Afzal, Fattahi Asieh Sadat, Gharib Masoumeh, Pasdar Alireza

机构信息

Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Egypt Natl Canc Inst. 2017 Dec;29(4):191-195. doi: 10.1016/j.jnci.2017.10.001. Epub 2017 Dec 7.

Abstract

PURPOSE

It is now well known that evading apoptosis, as a cancer hallmark, can lead to tumour initiation, progression and metastasis. As a result of genome wide association studies, an initiator protease in this pathway, caspase 8 (CASP8), has been found to be an important gene regarding breast cancer susceptibility. The alterations of the expression of this gene have been reported in breast cancer cell lines. Given that in previous studies expression analysis of this gene had only been done in breast cancer cell lines, in this study we aimed to evaluate the expression of this gene in breast cancer tissues versus adjacent normal tissues, using real-time quantitative method.

METHODS

Caspase 8 mRNA expression was quantified using comparative RT-qPCR in 27 fresh frozen breast tumours and 27 adjacent normal tissues. Moreover, relationship between the expression changes of CASP8 in tumour tissue and various clinical and pathological features were evaluated in an Iranian population.

RESULTS

The present study showed that expression of CASP8 was significantly reduced in tumour tissues compared to neighbouring normal tissues (p = .004). CASP8 expression was significantly correlated with the status of hormone receptors (ER and PR).

CONCLUSION

To the best of our knowledge, this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. Our data support previous results obtained from cell lines and therefore highlights the seminal role of the induction of CASP8 expression, as a novel therapeutic approach, in order to sensitize tumour cells to apoptotic stimuli.

摘要

目的

如今众所周知,逃避细胞凋亡作为一种癌症标志,可导致肿瘤的起始、进展和转移。全基因组关联研究结果显示,该通路中的起始蛋白酶半胱天冬酶8(CASP8)是与乳腺癌易感性相关的一个重要基因。已有报道称该基因在乳腺癌细胞系中的表达存在改变。鉴于以往研究仅在乳腺癌细胞系中进行了该基因的表达分析,本研究旨在采用实时定量方法评估该基因在乳腺癌组织与相邻正常组织中的表达情况。

方法

采用比较逆转录定量聚合酶链反应(RT-qPCR)对27例新鲜冷冻乳腺癌组织和27例相邻正常组织中的半胱天冬酶8信使核糖核酸(mRNA)表达进行定量。此外,在伊朗人群中评估了肿瘤组织中CASP8表达变化与各种临床和病理特征之间的关系。

结果

本研究表明,与相邻正常组织相比,肿瘤组织中CASP8的表达显著降低(p = 0.004)。CASP8表达与激素受体(雌激素受体和孕激素受体)状态显著相关。

结论

据我们所知,本研究是关于乳腺癌组织与相邻正常组织中CASP8表达降低的首次报道。我们的数据支持了先前从细胞系获得的结果,因此突出了诱导CASP8表达作为一种新的治疗方法,使肿瘤细胞对凋亡刺激敏感的重要作用。

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