Mass Spectrometry Centre, Organic Chemistry and Natural Products Research Unit, Department of Chemistry, Universidade de Aveiro, Campus de Santiago, Aveiro, Portugal; and.
Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA.
FASEB J. 2014 Oct;28(10):4247-64. doi: 10.1096/fj.14-249672. Epub 2014 Jun 26.
This work combined gene and protein expression, gas chromatography-flame ionization detector, and hydrophilic interaction liquid chromatography-tandem mass spectrometry to compare lipid metabolism changes in undifferentiated/proliferating vs. functionally differentiated mammary epithelial cells (MECs) and to study their correlation to breast cancer survival. Sixty-eight genes involved in lipid metabolism were changed in MEC differentiation. Differentiated cells showed induction of Elovl6 (2-fold), Scd1 (4-fold), and Fads2 (2-fold), which correlated with increased levels of C16:1 n-7 and C18:1 n-9 (1.5-fold), C20:3 n-6 (2.5-fold), and C20:4 n-6 (6-fold) fatty acids (FAs) and more phospholipids (PLs) containing these species. Further, increased expression (2- to 3-fold) of genes in phosphatidylethanolamine (PE) de novo biosynthesis resulted in a 20% PE increase. Proliferating/undifferentiated cells showed higher C16:0 (1.7-fold) and C18:2 n-6 (4.2-fold) levels and more PLs containing C16:0 FAs [PC(16:0/16:1), PG(16:0/18:2), PG(16:0/18:1), and SM(16:0/18:0)]. Kaplan-Meier analysis of data from 3455 patients with breast cancer disclosed a positive correlation for 59% of genes expressed in differentiated MECs with better survival. PE biosynthesis and FA oxidation correlated with better prognosis in patients with breast cancer, including the basal-like subtype. Therefore, genes involved in mammary gland FA and PL metabolism and their resulting molecular species reflect the cellular proliferative ability and differentiation state and deserve further studies as potential markers of breast cancer progression
这项工作结合了基因和蛋白质表达、气相色谱-火焰离子化检测器和亲水相互作用液相色谱-串联质谱，比较了未分化/增殖与功能分化的乳腺上皮细胞（MEC）中的脂质代谢变化，并研究了它们与乳腺癌生存的相关性。在 MEC 分化过程中，有 68 个与脂质代谢相关的基因发生了变化。分化后的细胞诱导了 Elovl6（2 倍）、Scd1（4 倍）和 Fads2（2 倍），这与 C16:1 n-7 和 C18:1 n-9（1.5 倍）、C20:3 n-6（2.5 倍）和 C20:4 n-6（6 倍）脂肪酸（FA）以及更多含有这些物质的磷脂（PL）水平的增加有关。此外，磷酸乙醇胺（PE）从头生物合成中基因表达的增加（2-3 倍）导致 PE 增加 20%。增殖/未分化的细胞显示出更高的 C16:0（1.7 倍）和 C18:2 n-6（4.2 倍）水平，以及更多含有 C16:0 FA 的 PL [PC（16:0/16:1）、PG（16:0/18:2）、PG（16:0/18:1）和 SM（16:0/18:0）]。对 3455 名乳腺癌患者的数据进行 Kaplan-Meier 分析表明，分化的 MEC 中表达的 59%的基因与更好的生存相关。PE 生物合成和 FA 氧化与乳腺癌患者的更好预后相关，包括基底样亚型。因此，参与乳腺 FA 和 PL 代谢及其产生的分子种类的基因反映了细胞的增殖能力和分化状态，值得进一步研究，作为乳腺癌进展的潜在标志物。
