Analyzing the regulation of metabolic pathways in human breast cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Schramm
Gunnar
G
Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, and Bioquant, University of Heidelberg, INF 267, 69120 Heidelberg, Germany.
Surmann
Eva-Maria
EM
Wiesberg
Stefan
S
Oswald
Marcus
M
Reinelt
Gerhard
G
Eils
Roland
R
König
Rainer
R
D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053858:Metabolic Networks and Pathways; D013256:Steroids / Q000096:biosynthesis; D015854:Up-Regulation
D001647:Bile Acids and Salts; D004967:Estrogens; D013256:Steroids