Cyclin E as molecular marker in the management of breast cancer: a review.
Cyclin E as molecular marker in the management of breast cancer: a review.
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发表时间：
2006-04
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通讯作者：
A. López-Beltran;G. MacLennan;R. Montironi
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作者：
A. López-Beltran;G. MacLennan;R. Montironi
在过去的十年中，许多分子标记物已被确定，可能在乳腺癌的发生和预后中发挥作用。临床实践中最常用的标志物是雌激素受体、孕激素受体和HER-2/neu。最近的研究发现，细胞周期蛋白E是一个有前途的乳腺癌预后指标，并检查其作为治疗靶点的潜力。进一步的研究表明，细胞周期蛋白E水平在细胞周期中是周期性的，蛋白质水平在G1期达到峰值。细胞周期蛋白E水平的这一峰值也与细胞周期蛋白E-cdk 2复合物的最大酶促功能相关，表明细胞周期蛋白E在调节G1期到S期转变中的关键作用。研究乳腺癌中细胞周期蛋白E改变的相关性的研究表明，在一些乳腺癌细胞系中的基因扩增，数据提供了强有力的支持细胞周期蛋白E在乳腺癌发生中的作用。据信，最显著的细胞周期蛋白E改变是全长细胞周期蛋白E翻译后裂解成低分子量形式，所述低分子量形式与50-kDa的全长蛋白质相比是高活性的，并且与乳腺癌的增加的阶段和等级相关。本文就细胞周期蛋白E在乳腺癌预后和治疗中的作用作一综述。
Over the past decade numerous molecular markers have been identified that may play a role in breast carcinogenesis and prognosis. The most commonly used markers in clinical practice are the estrogen receptor, progesterone receptor and HER-2/neu. Recent studies found cyclin E to be a promising prognostic indicator in breast cancer and examined its potential as a target for therapy. Further studies demonstrated that cyclin E levels were periodic during the cell cycle, with levels of protein peaking in the G1 phase. This peak in cyclin E levels also correlated with maximum enzymatic function of the cyclin E-cdk2 complex, suggesting a critical role of cyclin E in regulating G1 to S-phase transition. Studies examining the relevance of cyclin E alterations in breast cancer have shown gene amplifications in some breast cancer cell lines, data that provide strong support for the role of cyclin E in breast carcinogenesis. It is believed that the most significant cyclin E alteration is post-translational cleavage of full-length cyclin E into low molecular weight forms that are hyperactive compared to the 50-kDa, full-length protein and correlate with increasing stage and grade of breast cancer. The role of cyclin E in the prognosis and therapy of breast cancer is reviewed according to recent publications.