Transcriptomics provides the tool for deciphering gene expression networks, and proteomics links these networks to protein products. The third crucial partner is metabolomics, which defines the metabolic network(s) linked to gene expression. NMR and mass spectrometry enable the broad screen analysis of the metabolome and its transformation pathways, transcending classical targeted metabolic studies. These tools were combined to investigate the anticancer mechanisms of different selenium forms in human lung cancer cells. Using 2-D NMR and tandem-MS, we mapped perturbations of 13C labeling patterns in numerous metabolites induced by selenite and selenomethionine. This information was used to interpret selenite-induced changes in gene expression networks. Linking metabolic dysfunctions to altered gene expression profiles provided new insights into the regulatory network underlying the metabolic dysfunctions, enabled the assembly of discrete gene expression events into functional pathways, and revealed protein targets for proteomic analysis.
|Number of pages||26|
|Journal||Drug Metabolism Reviews|
|State||Published - Jul 1 2006|
Bibliographical noteFunding Information:
This work was supported in part by the Kentucky Lung Cancer Research Program grant #04-0256, NCI grant #1 R01 CA101199-01, the Brown Foundation and NSF EPS-CoR grant #EPS-0447479. We gratefully acknowledge technical assistance from V. Arumugam, Anna Tchernatynskaia, Dr. S. Arumugam, and Dr. Laura Bandura.
- C isotopomer profiling
- GC-tandem MS
- Lung adenocarcinoma A549 cells
- Two-dimensional NMR
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics (all)
- Pharmacology (medical)