Investigating the Role of the CPT1A pathway in breast tumor proliferation (2016)

Undergraduate: Pranavi Sanka

Faculty Advisor: Charles Perou
Department: Biology

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Breast cancer is the second most lethal form of cancer in women, accounting for more than 230,000 new cases in the United States annually. Highly proliferative tumors are more aggressive and these patients generally have a poor prognosis since they largely fail to respond to current therapeutic regimens.

Recent work by the Perou lab identified the CPT1A gene to be uniquely amplified and essential for viability in highly proliferative, hormone receptor positive breast cancers, representing a potential therapeutic target. CPTA1 is an enzyme involved in fatty acid oxidation which leads to energy production. While normal cells use glycolysis as their main mode of energy production, our data suggest that tumor cells with CPT1A amplification depend on fatty acid oxidation. To study the CPT1A pathway, I used two highly proliferative luminal CPT1A amplified cell lines and another less proliferative, CPT1A non-amplified cell line as a control. All cells were treated with the CPT1A-specific drug, etomoxir (1 nM -10 ¿¿M), and proliferation levels were measured. The IC50 values (concentration when proliferation decreased by 50%) for the two CPT1A amplified cell lines at 366 and 249 ¿¿M were significantly lower than the control¿¿¿s IC50 value of 1183 ¿¿M, which shows that the CPT1A amplified cell lines depend on the CPT1A pathway for cellular proliferation, whereas normal cells do not. This offers promising results as we can continue with studies to create drugs that target this gene pathway.