Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models.
Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models.
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DOI：
10.1186/1471-2407-10-433
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发表时间：
2010-08-17
期刊：
影响因子：
3.8
通讯作者：
Gribbestad IS
中科院分区：
文献类型：
--
作者：
Moestue SA;Borgan E;Huuse EM;Lindholm EM;Sitter B;Børresen-Dale AL;Engebraaten O;Maelandsmo GM;Gribbestad IS
在乳腺癌中经常观察到含胆碱化合物的浓度增加，并且可以作为诊断和治疗监测目的的生物标志物。然而，胆碱代谢异常的潜在机制知之甚少。胆碱衍生的代谢产物的浓度测定在异种移植的原发性人乳腺癌，基底样和管腔样亚型。使用高分辨率魔角旋转磁共振波谱（HR MAS MRS）对新鲜冷冻组织中的代谢物进行定量。从全基因组表达微阵列分析中检索参与磷脂酰胆碱（PtdCho）代谢的基因的表达。将异种移植物的代谢物谱与从雌激素/孕激素受体阳性（ER+/PgR+）或三阴性（ER-/PgR-/HER 2-）乳腺癌患者中取样的人乳腺癌的代谢物谱进行比较。在基底样异种移植物中，甘油磷酸胆碱（GPC）浓度高于磷酸胆碱（PCo）浓度，而这种模式在管腔样异种移植物中逆转。这些差异可能是由于胆碱激酶（CHKA，CHKB）表达降低以及基底样模型中磷脂酶A2组4A（PLA 2G 4A）和磷脂酶B1（PLB 1）表达升高介导的PtdCho降解升高。在基底样模型中甘氨酸浓度较高。虽然甘氨酸可能来自能量代谢途径，但基因表达数据表明在基底样异种移植物中从PtdCho合成到甘氨酸形成的代谢转变。与异种移植模型的结果一致，来自三阴性乳腺癌的组织样品具有比来自ER+/PgR+癌的样品更高的GPC/PCho比率，表明实验模型中的胆碱代谢代表管腔样和基底样人乳腺癌。胆碱代谢物浓度的差异与基因表达的差异很好地对应，表明在代表基底样和管腔样乳腺癌的异种移植模型中有不同的代谢谱。在ER+/PgR+和三阴性乳腺癌的患者材料中也观察到胆碱代谢物谱的相同特征，表明异种移植物是研究腔样和基底样乳腺癌中胆碱代谢的相关模型系统。
Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite concentrations corresponded well with differences in gene expression, demonstrating distinct metabolic profiles in the xenograft models representing basal-like and luminal-like breast cancer. The same characteristics of choline metabolite profiles were also observed in patient material from ER+/PgR+ and triple-negative breast cancer, suggesting that the xenografts are relevant model systems for studies of choline metabolism in luminal-like and basal-like breast cancer.
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影响因子：
2.9
作者：
Morse, David L.;Carroll, Danielle;Day, Sam;Gray, Heather;Sadarangani, Pooja;Murthi, Shiva;Job, Constantin;Baggett, Brenda;Raghunand, Natarajan;Gillies, Robert J.
通讯作者：
Gillies, Robert J.
在412例患者的基于人群的队列中，乳腺癌的固有分子特征。
影响因子：
7.4
作者：
Calza, Stefano;Hall, Per;Auer, Gert;Bjohle, Judith;Klaar, Sigrid;Kronenwett, Ulrike;T Liu, Edison;Miller, Lance;Ploner, Alexander;Smeds, Johanna;Bergh, Jonas;Pawitan, Yudi
通讯作者：
Pawitan, Yudi
影响因子：
6.4
作者：
Eliyahu, Galit;Kreizman, Tamar;Degani, Hadassa
通讯作者：
Degani, Hadassa
影响因子：
11.2
作者：
Glunde, K;Jie, C;Bhujwalla, ZM
通讯作者：
Bhujwalla, ZM
影响因子：
3.9
作者：
Kurebayashi, Junichi;Moriya, Takuya;Nakashima, Kazutaka
通讯作者：
Nakashima, Kazutaka