Phosphoproteomic profiling of breast cancer cell lines
EMSL Project ID
30462
Abstract
Breast cancer is a very heterogeneous disease, consisting of different molecular subtypes. Effective, targeted treatment is available for estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) positive tumors. However, ~15% of breast tumors are negative for ER, HER2 and progesterone receptor (PgR), the so-called triple negative (TN) subtype. For this group of tumors no targeted treatment is available at present, and prognosis is poor. A possible target for therapy in TN breast cancer is the tyrosine kinase epidermal growth factor receptor (EGFR) protein, which is specifically overexpressed in this subtype. Activated EGFR phosphorylates downstream signaling proteins, resulting in growth stimulation, which can be effectively blocked by therapeutic kinase inhibitors, as was previously shown in other types of cancer. In this study, we propose to investigate the phosphorylation dynamics of dozen of previously identified, target proteins in different breast cancer cell lines grown in the absence and presence of therapeutic kinase inhibitors. Phosphoproteins will be enriched from a total cell lysate, and further analyzed by a unique integrated bottom-up and top-down approach, developed at EMSL, to identify multiple phosphorylated isoforms of intact proteins.
Monitoring multisite protein phosphorylation in breast cancer cell lines will reveal potential targets for the development of new therapies. This will in addition aid in the identification of a protein phosphorylation pattern that correlates with a good response to therapeutic kinase inhibitors, which may in the future be useful as a pre-diagnostic prediction tool.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2009-01-01
End Date
2009-09-30
Status
Closed
Released Data Link
Team
Principal Investigator