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Attenuation of ZnT2 in tumorigenic breast cancer cells results in apoptosis
Author(s) -
Foolad Farnaz,
Lopez Veronica,
Kelleher Shan L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.922.5
Subject(s) - apoptosis , breast cancer , cancer research , cancer cell , biology , mitochondrion , programmed cell death , cancer , chemistry , microbiology and biotechnology , biochemistry , genetics
Zinc (Zn) levels are elevated in breast tumor biopsies. Regulation of mitochondrial Zn metabolism controls intrinsic apoptosis, which is dysregulated in breast cancer. ZnT2 imports Zn into vesicles and mitochondria in breast cells. Our objective was to determine if altered ZnT2 expression in breast cancer cells affect the apoptotic pathways. To explore functional differences, we first determined that tumorigenic breast cancer cells (T47D) have higher cellular Zn levels compared with normal breast cells (HC11). Interestingly, ZnT2 protein abundance was 10‐fold lower in tumor cells. Mitochondrial Zn levels (RhodZin‐3 fluorescence) were 30% lower in tumor cells. ZnT2‐attenuation in cancer cells reduced mitochondrial Zn pools further by ~30%. This resulted in a ~40% decrease in cell viability in tumor cells which did not occur in normal cells. Decreased cell number was associated with increased Annexin‐V staining, illustrating that tumor cell death resulted from apoptosis and not necrosis. In conclusion, our results suggest that under‐expression of ZnT2 in tumor cells reduces the ability of breast cells to modulate mitochondrial Zn level to regulate the apoptotic threshold. Statistics indicate that >200,000 new cases and deaths result from breast cancer annually, thus development of new and innovative therapies is critical. Results from our study suggest that ZnT2 may be a potential therapeutic target.