Abstract
BackgroundTumor 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.MethodsFor 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.ResultsBesides 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.ConclusionWe 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.
Highlights
Tumor therapy mainly attacks the metabolism to interfere the tumor’s anabolism and signaling of proliferative second messengers
We revealed 19 significant metabolic pathways including increased purine and pyrimidine biosynthesis which were needed for increased mitosis cycles
We revealed less expected differentially regulated pathways, such as biosynthesis of steroids and bile acids
Summary
Tumor therapy mainly attacks the metabolism to interfere the tumor’s anabolism and signaling of proliferative second messengers. We investigated tumor specific regulation in the metabolism of breast cancer. Breast cancer patients with the same stage of disease can have very different treatment responses and overall outcome. Clinical predictive factors like age, tumor size, lymph node status, histological and pathological grade or hormone-receptor status, often fail to accurately predict clinical outcome, distant metastasis and recurrence of the cancer. A more accurate means of prognosis and selection of therapy would substantially improve disease-free and overall survival of breast cancer patients [5]. Cancer cells acquire their hallmarks of malignancy through the accumulation of advantageous gene activation and inactivation events over long periods of time [6]. A long-standing strategy for cancer treatment is to attack basic tumor metabolism by inhibiting nucleotide biosynthesis [7,8] and DNA production [9]
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