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首页> 外文期刊>Cell cycle >Low molecular weight cyclin E is specific in breast cancer and is associated with mechanisms of tumor progression.
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Low molecular weight cyclin E is specific in breast cancer and is associated with mechanisms of tumor progression.

机译:低分子量细胞周期蛋白E在乳腺癌中具有特异性,并且与肿瘤进展的机制有关。

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摘要

Low molecular weight (LMW) isoforms of cyclin E are post-translationally generated in breast cancer cells and are associated with aggressive disease and poor prognosis. In this study, the specificity of LMW cyclin E to cancer cells was determined by measuring cyclin E expression in tumor and non-tumor tissue from 340 breast cancer patients. Our results reveal the LMW isoforms were detected significantly more frequently in breast tumor tissue than in adjacent non-tumor breast tissues (p < 0.0001). The biologic consequences of the LMW isoforms were studied using a non-tumorigenic mammary epithelial cell line transfected with the cyclin E isoforms and resulted in increased clonogenicity, the inability to enter quiescence in response to growth factor deprivation and genomic instability compared to the full-length cyclin E. Biochemical differences between the full-length and the LMW isoforms were also evident. Biacore analyses show that the LMW isoforms have more efficient binding to CDK2 compared to full-length cyclin E, which could account for the unique biologic consequences observed with the expression of LMW cyclin E. The LMW isoforms of cyclin E are tumor specific, and are biochemically and biologically distinct from the full-length cyclin E which could provide a novel role in breast cancer progression.
机译:Cyclin E的低分子量(LMW)亚型在乳腺癌细胞中翻译后产生,与侵袭性疾病和不良预后有关。在这项研究中,通过测量340例乳腺癌患者的肿瘤和非肿瘤组织中的细胞周期蛋白E表达,确定了LMW细胞周期蛋白E对癌细胞的特异性。我们的结果表明,与相邻的非肿瘤乳腺组织相比,在乳腺肿瘤组织中发现LMW亚型的频率更高(p <0.0001)。与非全长乳腺上皮细胞系细胞周期蛋白E亚型转染相比,LMW亚型的生物学后果进行了研究,与全长相比,克隆性提高,克隆性增强,无法响应生长因子剥夺和基因组不稳定性而进入静止状态全长和LMW亚型之间的生化差异也很明显。 Biacore分析表明,与全长细胞周期蛋白E相比,LMW同工型与CDK2的结合更有效,这可以解释LMW细胞周期蛋白E的表达所观察到的独特生物学后果。在生物学上和生物学上不同于全长细胞周期蛋白E,后者可以在乳腺癌的进展中提供新的作用。

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