ATTENUATION OF MITOCHONDRIAL ZINC IMPORT THROUGH ZnT2 IN TUMORIGENIC BREAST CANCER CELLS RESULTS IN APOPTOSIS
Open Access
- Author:
- Foolad, Farnaz
- Area of Honors:
- Nutritional Sciences
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Shannon Leanne Kelleher, Thesis Supervisor
Shannon Leanne Kelleher, Thesis Supervisor
Rebecca L Corwin, Thesis Honors Advisor - Keywords:
- zinc
breast cancer
apoptosis
znt2 - Abstract:
- Statistics indicate that ~200,000 new cases and deaths result from breast cancer annually, yet much about the development and progression of the disease remains unknown. Previous studies link breast cancer with dysregulated zinc (Zn) metabolism at the systemic and cellular level. Our first objective was to characterize the dysregulation of Zn levels and intracellular Zn distribution in human tumorigenic breast cancer cells (T47D). Secondly, we aimed to further explore the relationship between high cellular Zn levels, breast cancer, and the role of the Zn transporter ZnT2. Our results were consistent with data illustrating high Zn concentrations in breast tumor cells compared with normal mammary cells (HC11). Interestingly, our assessment of Zn distribution in breast tumor cells indicated abnormally low endogenous mitochondrial Zn levels. Upon evaluation of ZnT2 protein expression, we found ZnT2 protein abundance to be lower in breast tumor cells compared with normal cells. Similar to normal breast cells, our data indicated ZnT2 localization to the inner mitochondrial membrane in breast tumor cells, indicating that ZnT2 is a mitochondrial Zn importer in tumor cells. The reduction of mitochondrial Zn import through ZnT2 attenuation reduced mitochondrial Zn levels beyond the apoptotic threshold, as indicated by increased Annexin-V staining. Furthermore, ZnT2-attenuation resulted in decreased cellular proliferation and tumorigenicity of breast tumor cells. In conclusion, our study suggests the reduction of ZnT2 expression results in the depletion of mitochondrial Zn, impeding vital mitochondrial functions and thus inducing cellular destruction through the activation of the apoptotic pathway in breast cancer cells. We believe our results suggest a promising future role for ZnT2 as a potential therapeutic target for the treatment of breast cancer. ZnT2 presents both a tissue-specific and malignant-specific target, and may prove to be both a safe and effective form of treatment specifically for breast cancer. Our ongoing studies will further develop the potential for ZnT2 as a targeted treatment, in hopes of finding a cure for this deadly cancer that affects so many women.