(182d) Inference of Predominant Pathways In Cancer: A Proteomic Study Among Three Human Mammary Epithelial Cell Models

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 objective of this study was to quantify alterations in protein expression in three cellular models of breast cancer and infer differentially regulated signaling pathways associated with the hallmarks of cancer. 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). Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. We observed cell motility pathways to be predominantly associated with BT474 cell line, whereas amino acid metabolism pathways were associated with SKBR3 cell line. While “protein ubiquitination” and “apoptosis signaling” pathways were common to both the cell lines, the observed patterns of protein expression and post-translational modification suggest that the evasion of apoptosis in the tumorigenic cell lines occurs via different mechanisms.