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在激素阳性乳腺癌组织中体内检测到一种罕见的类二十碳烷酸前体类似物,即齐墩果酸(5Z,11Z,14Z-20:3)。

A rare eicosanoid precursor analogue, sciadonic acid (5Z,11Z,14Z-20:3), detected in vivo in hormone positive breast cancer tissue.

机构信息

Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Dell Pediatric Research Institute and Dept. of Pediatrics, Dell Medical School, The University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX 78723, USA.

Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2018 Jul;134:1-6. doi: 10.1016/j.plefa.2018.05.002. Epub 2018 May 16.

Abstract

Numerous genetic alterations of HSA 11q13 are found frequently in several cancer types, including breast cancer (BC). The 11q13 locus harbors FADS2 encoding Δ6 desaturation which is not functional in several cancer cell lines, including hormone positive MCF7 BC cells. In vitro, the non-functional FADS2 activity unmasks 18:2n-6 elongation to 20:2n-6 and Δ5 desaturation by FADS1 to yield 5Z,11Z,14Z-20:3 (sciadonic acid) rather than 5Z,8Z,11Z,14Z-20:4 (arachidonic acid). In this pilot study we aimed to determine whether 5,11,14-20:3 appears in vivo in hormone positive human BC tissue. Fatty acids were profiled in surgically removed human breast tumor and adjacent normal tissue (n = 9). Sciadonic acid was detected in three of nine breast tumor samples and was below detect limits in normal breast tissue. The internal Δ8 double bond of arachidonic acid is required for normal eicosanoid synthesis but is missing in sciadonic acid. This pilot study demonstrates for the first time in vivo sciadonic acid in hormone positive BC tissue, warranting a larger survey study to further evaluate its appearance and the functional implications.

摘要

在包括乳腺癌 (BC) 在内的多种癌症类型中,经常发现 HSA 11q13 的许多基因改变。11q13 基因座含有编码 Δ6 去饱和的 FADS2,但在包括激素阳性 MCF7 BC 细胞在内的几种癌细胞系中没有功能。在体外,非功能性 FADS2 活性使 18:2n-6 延伸为 20:2n-6 和 FADS1 的 Δ5 去饱和,生成 5Z,11Z,14Z-20:3(亚油酸),而不是 5Z,8Z,11Z,14Z-20:4(花生四烯酸)。在这项初步研究中,我们旨在确定激素阳性人类 BC 组织中是否存在 5,11,14-20:3。对手术切除的人乳腺癌组织和相邻正常组织中的脂肪酸进行了分析(n=9)。在 9 个乳腺癌样本中的 3 个中检测到亚油酸,而在正常乳腺组织中低于检测限。花生四烯酸的内部 Δ8 双键是正常类二十烷酸合成所必需的,但在亚油酸中缺失。这项初步研究首次在激素阳性 BC 组织中体内证实了亚油酸的存在,需要进行更大规模的调查研究以进一步评估其出现及其功能意义。

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