Role of lifeguard β-isoform in the development of breast cancer.

Role of lifeguard β-isoform in the development of breast cancer.
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DOI:
10.3892/or.2014.3363
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发表时间:
2014-10
期刊:
影响因子:
4.2
通讯作者:
Bucan V
Bucan V
中科院分区:
医学3区
文献类型:
--
作者:
Dastagir N;Lazaridis A;Dastagir K;Reimers K;Vogt PM;Bucan V

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在上个世纪,通过改进药物和放射疗法以及手术技术,在治疗乳腺癌方面取得了很大进展。尽管如此,乳腺癌仍然是欧洲和美国妇女死亡的主要原因。乳腺癌在细胞水平上的原因仍然没有完全了解。在本研究中,我们研究了乳腺癌组织中Lifeguard β-亚型的表达。与Lifeguard相比,β-同种型少了一个跨膜结构域,这是七个跨膜结构域中的最后一个(99 bp),因此我们怀疑Lifeguard β-同种型表现出不同的功能。我们确定了Lifeguard β-亚型在乳腺癌细胞系(MCF-7和MDA-MB-231)、人乳腺上皮细胞系(MCF 10A)和乳腺肿瘤组织切片中的表达和功能。采用Western blotting、PCR芯片和免疫荧光技术检测Lifeguard及其β-亚型的表达。此外,我们研究了Lifeguard β-异构体表达抑制Fas诱导的细胞凋亡的能力。我们的结果表明,救生员β-异构体在乳腺肿瘤组织中强烈表达。更值得注意的是,我们证明了Fas敏感性在表达Lifeguard β-同种型的MCF 10A乳腺细胞中降低。综上所述,我们的研究结果表明了Lifeguard β-同种型作为抗凋亡蛋白的作用,并进一步证明了Lifeguard β-同种型作为开发新型治疗策略的靶点的潜力。
In the last century there has been great progress in the treatment of breast cancer by improving drug and radiation therapy as well as surgical techniques. Despite this development, breast cancer remains a major cause of death among women in Europe and the US. The cause of breast cancer at the cellular level is still not fully understood. In the present study, we investigated the expression of the Lifeguard β-isoform in breast cancer tissues. In contrast to Lifeguard, the β-isoform has one transmembrane domain less, which is the last of seven (99 bp), and due to this we suspect that the Lifeguard β-isoform exhibits a different function. We determined the expression and function of the β-isoform of Lifeguard in breast cancer cell lines (MCF-7 and MDA-MB-231), a human breast epithelial cell line (MCF10A) and in breast tumour tissue sections. Western blotting, PCR arrays and immunofluorescence were used to investigate the expression of Lifeguard and its β-isoform. Moreover, we investigated the ability of Lifeguard β-isoform expression to inhibit apoptosis induced by Fas. Our results indicated that Lifeguard β-isoform is strongly expressed in breast tumour tissues. More notably, we demonstrated that Fas sensitivity was reduced in the MCF10A breast cells expressing the Lifeguard β-isoform. Taken together, our findings indicate the role of the Lifeguard β-isoform as an anti-apoptotic protein and provide further evidence of the potential of the Lifeguard β-isoform as a target for the development of novel therapeutic strategies.
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发表时间: 2009-09-14
期刊: Journal of experimental & clinical cancer research : CR
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期刊: APOPTOSIS
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