Journal
JOURNAL OF PROTEOME RESEARCH
Volume 16, Issue 9, Pages 3277-3286Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.7b00283
Keywords
MCF-7; BT-474; MDA-MB-468; protein folding; chemical denaturation
Categories
Funding
- National Institutes of General Medical Sciences at the National Institutes of Health [2R01GM084174-07]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available