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通过(31)P MRS监测发现,甘油磷酸胆碱磷酸二酯酶GDPD5的沉默改变了体内乳腺癌模型中的磷脂代谢物谱。

Silencing of the glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by (31) P MRS.

作者信息

Wijnen J P, Jiang L, Greenwood T R, Cheng M, Döpkens M, Cao M D, Bhujwalla Z M, Krishnamachary B, Klomp D W J, Glunde K

机构信息

The Johns Hopkins University In vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands.

出版信息

NMR Biomed. 2014 Jun;27(6):692-9. doi: 10.1002/nbm.3106. Epub 2014 Apr 24.

Abstract

Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus ((31) P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors.

摘要

异常的胆碱磷脂代谢是癌症新出现的一个标志,它与癌症发生及肿瘤进展有关。恶性代谢表型的特征是侵袭性乳腺癌细胞中磷酸胆碱(PC)水平高而甘油磷酸胆碱(GPC)水平相对低。磷(³¹P)磁共振波谱能够非侵入性地检测这些胆碱的水溶性代谢物以及乙醇胺磷脂代谢。在此,我们研究了在MDA-MB-231乳腺癌细胞和原位肿瘤异种移植物中稳定沉默含甘油磷酸二酯酶结构域5(GDPD5)的影响,GDPD5是一种具有甘油磷酸胆碱磷酸二酯酶活性的酶。与对照肿瘤相比,用GDPD5特异性短发夹RNA稳定沉默GDPD5的肿瘤中GPC和磷酸乙醇胺(PE)水平升高。

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Stromal cells in tumor microenvironment and breast cancer.肿瘤微环境中的基质细胞与乳腺癌。
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Glycerophosphocholine (GPC) is a poorly understood biomarker in breast cancer.甘油磷酸胆碱(GPC)是一种在乳腺癌中了解甚少的生物标志物。
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):E2506; author reply E2507. doi: 10.1073/pnas.1208226109. Epub 2012 Jul 31.
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