Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies
Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies
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DOI：
10.1002/ijc.22293
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发表时间：
2007-04-15
影响因子：
6.4
通讯作者：
Degani, Hadassa
中科院分区：
文献类型：
--
作者：
Eliyahu, Galit;Kreizman, Tamar;Degani, Hadassa
发现有助于改善乳腺癌检测和诊断的代谢和分子标记是一个需要实现的重要目标。乳腺病变磁共振波谱中的高复合胆碱信号已被证明可以提高乳腺癌诊断的准确性。在本研究中，我们揭示了与正常人乳腺上皮细胞相比，人乳腺癌细胞系中与诱导胆碱代谢和磷酸胆碱积累相关的主要分子和生化步骤。我们发现，与正常乳腺上皮细胞相比，癌细胞中特定胆碱转运蛋白：有机阳离子转运蛋白-2和胆碱高亲和力转运蛋白-1以及胆碱激酶α的表达水平上调。胆碱转运蛋白like-1、有机阳离子转运蛋白-1和胆碱激酶P在正常细胞和癌细胞中的表达水平相似。我们进一步表明，癌细胞中的胆碱转运率和胆碱激酶活性确实增加了几倍，导致磷酸磷脂酰胆碱升高。结果强烈表明，磷酸胆碱可以作为乳腺癌的生物标志物，反映特定胆碱转运蛋白和胆碱激酶基因的上调。 (c) 2007 年 Wiley-Liss, Inc.
The discovery of metabolic and molecular markers that help improving the detection and diagnosis of breast cancer is an important goal to be achieved. A high composite-choline signal in magnetic resonance spectra of breast lesions has been demonstrated to improve the accuracy of breast cancer diagnosis. In the present study we revealed the principal molecular and biochemical steps associated with the induction of choline metabolism and phosphrocholine accumulation in human breast cancer cell-lines in comparison with normal human mammary epithelial cells. We found upregulation of the expression levels of specific choline transporters: organic cation transporter-2 and choline high affinity transporter-1, as well as of the enzyme choline kinase alpha in the cancerous cells in comparison with that in the normal mammary epithelial cells. The expression levels of choline transporter like-1, organic cation transporter-1 and choline kinase P were similar in normal and cancerous cells. We further showed that choline transport rates and choline kinase activity indeed increased by several fold in the cancer cells leading to the elevation of phosphotholine. The results strongly suggest that phosphocholine can serve as a biomarker of breast cancer reflecting upregulation of specific choline transporters and choline kinase genes. (c) 2007 Wiley-Liss, Inc.