Analyzing the regulation of metabolic pathways in human breast cancer.
Analyzing the regulation of metabolic pathways in human breast cancer.
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DOI：
10.1186/1755-8794-3-39
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发表时间：
2010-09-10
影响因子：
2.7
通讯作者：
König R
中科院分区：
文献类型：
--
作者：
Schramm G;Surmann EM;Wiesberg S;Oswald M;Reinelt G;Eils R;König R
肿瘤的治疗主要是通过攻击代谢来干扰肿瘤的生长和增殖第二信使的信号转导。然而，不同癌症的代谢需求是非常异质的，并且取决于它们的组织来源、年龄、性别和其他临床参数。我们研究了乳腺癌代谢中的肿瘤特异性调节。为此，我们将来自微阵列的基因表达数据映射到相应的酶及其代谢反应网络上。我们使用Haar小波变换对代谢途径的最佳排列网格表示作为模式识别方法来检测网络中相邻酶的协调调节。使用显著的组合表达模式来选择显示侵袭性肿瘤的改变调节的代谢途径。除了能量产生和核苷酸合成的上调外，我们还发现了类固醇和胆汁酸生物合成相互作用的有趣细胞开关。类固醇的生物合成被上调用于雌激素合成，而雌激素合成是乳腺癌中增殖信号传导所需的。反过来，类固醇前体的分解被胆汁酸途径的下调所阻断。我们应用智能模式识别方法来分析代谢的调节，并阐明了人类乳腺癌在胆固醇生物合成和胆汁酸代谢的相互作用中的实质性调节，从而指向特定的乳腺癌治疗。
Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors. Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway. We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.
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影响因子：
3.3
作者：
Pai, R;Tarnawski, AS;Tran, T
通讯作者：
Tran, T
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
3.2
作者：
Gordi, T;Khamis, H
通讯作者：
Khamis, H