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与子宫平滑肌瘤中细胞增殖和负性凋亡调节相关的伴侣蛋白失调。

Dysregulated chaperones associated with cell proliferation and negative apoptosis regulation in the uterine leiomyoma.

作者信息

Ura Blendi, Scrimin Federica, Arrigoni Giorgio, Aloisio Michelangelo, Monasta Lorenzo, Ricci Giuseppe

机构信息

Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', I-34137 Trieste, Italy.

Department of Biomedical Sciences, University of Padua, I-35122 Padua, Italy.

出版信息

Oncol Lett. 2018 May;15(5):8005-8010. doi: 10.3892/ol.2018.8325. Epub 2018 Mar 22.

Abstract

Uterine leiomyomas are benign smooth muscle cell tumors that originate from the myometrium. In this study we focus on dysregulated chaperones associated with cell proliferation and apoptosis. Paired tissue samples of 15 leiomyomas and adjacent myometria were obtained and analyzed by two-dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification and western blotting for 2-DE data validation. The values of 6 chaperones were found to be significantly different in the leiomyoma when compared with the myometrium. A total of 4 proteins were upregulated in the leiomyoma and 2 proteins were downregulated. Calreticulin and 78 kDa glucose-regulated protein were further validated by western blotting because the first is considered a marker of cell proliferation, while the second protects against apoptotic cell death. In addition, we also validated the two downregulated proteins heat shock protein β-1 and heat shock 70 kDa protein 1A. Our study shows the existence of a dysregulation of chaperone proteins associated with leiomyoma development. Functional studies are needed to ascertain the role of these chaperones in the leiomyoma. This may be crucial for the further development of specific inhibitors against the activity of these proteins in order to block the growth of the leiomyoma.

摘要

子宫平滑肌瘤是起源于子宫肌层的良性平滑肌细胞肿瘤。在本研究中,我们关注与细胞增殖和凋亡相关的伴侣蛋白失调情况。获取了15例平滑肌瘤及其相邻子宫肌层的配对组织样本,并通过二维凝胶电泳(2-DE)进行分析。采用质谱法进行蛋白质鉴定,并用蛋白质印迹法对2-DE数据进行验证。结果发现,与子宫肌层相比,平滑肌瘤中6种伴侣蛋白的值存在显著差异。平滑肌瘤中有4种蛋白质上调,2种蛋白质下调。通过蛋白质印迹法进一步验证了钙网蛋白和78 kDa葡萄糖调节蛋白,因为前者被认为是细胞增殖的标志物,而后者可防止细胞凋亡死亡。此外,我们还验证了两种下调的蛋白质热休克蛋白β-1和热休克70 kDa蛋白1A。我们的研究表明,与平滑肌瘤发展相关的伴侣蛋白存在失调现象。需要进行功能研究以确定这些伴侣蛋白在平滑肌瘤中的作用。这对于进一步开发针对这些蛋白质活性的特异性抑制剂以阻断平滑肌瘤的生长可能至关重要。

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