Document Type
Article
Publication Date
2012
College/Unit
Statler College of Engineering and Mining Resources
Department/Program/Center
Chemical and Biomedical Engineering
Abstract
Background
A contemporary view of the cancer genome reveals extensive rearrangement compared to normal cells. Yet how these genetic alterations translate into specific proteomic changes that underpin acquiring the hallmarks of cancer remains unresolved. The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer.
Results
A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. We observed "protein ubiquitination" and "apoptosis signaling" pathways were both enriched in the two breast cancer models while "IGF signaling" and "cell motility" pathways were enriched in BT474 and "amino acid metabolism" were enriched in the SKBR3 cell line.
Conclusion
While "protein ubiquitination" and "apoptosis signaling" pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared to 184A1.
Digital Commons Citation
Kulkarni, Yogesh M. and Klinke, David J., "Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer" (2012). Faculty & Staff Scholarship. 2723.
https://researchrepository.wvu.edu/faculty_publications/2723
Source Citation
Kulkarni, Y.M., Klinke, D.J. Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer. Proteome Sci 10, 11 (2012). https://doi.org/10.1186/1477-5956-10-11
Comments
© 2012 Kulkarni and Klinke; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.