Large-Scale Analysis of Breast Cancer-Related Conformational Changes in Proteins Using SILAC-SPROX.
Proteomic methods for disease state characterization and biomarker discovery have traditionally utilized quantitative mass spectrometry methods to identify proteins with altered expression levels in disease states. Here we report on the large-scale use of protein folding stability measurements to characterize different subtypes of breast cancer using the stable isotope labeling with amino acids in cell culture and stability of proteins from rates of oxidation (SILAC-SPROX) technique. Protein folding stability differences were studied in a comparison of two luminal breast cancer subtypes, luminal-A and -B (i.e., MCF-7 and BT-474 cells, respectively), and in a comparison of a luminal-A and basal subtype of the disease (i.e., MCF-7 and MDA-MB-468 cells, respectively). The 242 and 445 protein hits identified with altered stabilities in these comparative analyses included a large fraction with no significant expression level changes. This suggests thermodynamic stability measurements create a new avenue for protein biomarker discovery. A number of the identified protein hits are known from other biochemical studies to play a role in tumorigenesis and cancer progression. This not only substantiates the biological significance of the protein hits identified using the SILAC-SPROX approach, but it also helps elucidate the molecular basis for their disregulation and/or disfunction in cancer.
Duke Scholars
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Related Subject Headings
- Thermodynamics
- Proteome
- Protein Stability
- Protein Folding
- Oxidation-Reduction
- Neoplasm Proteins
- MCF-7 Cells
- Isotope Labeling
- Hydrogen Peroxide
- Humans
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Thermodynamics
- Proteome
- Protein Stability
- Protein Folding
- Oxidation-Reduction
- Neoplasm Proteins
- MCF-7 Cells
- Isotope Labeling
- Hydrogen Peroxide
- Humans