Zinc Metabolism and Breast Disease
Breast cancer is the second leading cause of death in women. Approximately 270,000 women were diagnosed with breast cancer this year alone and according to the Susan G. Komen Foundation (http://ww5.komen.org/) one woman dies from breast cancer every 69 seconds. Moreover, ~50% of women of childbearing age suffer from a condition known as fibrocystic breast disease; the etiology of which is not understood and limited therapies are available. This clearly highlights the urgent demand to understand the complex mechanisms responsible for breast disease and to develop and validate novel, predictive markers for breast disease/cancer diagnosis, prognosis and therapy selection. Mounting evidence links dysregulated zinc transport in the breast with the transition and/or progression of breast disease. As an example, breast tumors hyper-accumulate zinc. This is further evidenced by aberrant expression of zinc transporting proteins that are responsible for maintaining zinc homeostasis in breast cancer biopsies from women and in cultured cell models. While these data illustrate the importance of tight regulation of zinc transport on mammary gland function the relationship between breast cancer etiology and abnormal zinc transport regulation or aberrant cellular functions remains unclear.
Our laboratory explores the relationship between aberrant zinc transporting mechanisms and their role in apoptosis, tumorigenesis and metastasis with the long-term goal of developing novel therapies for breast cancer treatment. We utilize cultured cell models, xenograft mouse models and human tumor biopsies to understand his complex process in humans. Our recent investigations determined that the profile of zinc transporter expression in breast cancer sub-types is different from that of non-malignant cells. For example, several zinc transporters including ZnT2 are over-expressed in cultured tumor cells and human tumor biopsies (Figure 3). Current studies aim to understand the mechanisms responsible for these differences and the relevance of these observations as it pertains to sub-type specific phenotypes.
Figure 3. ZnT2 is over-expressed in human breast tumor biopsies. Abundant expression of ZnT2 (black) is noted by immunostaining biopsied breast tumor tissue. Over-expression of ZnT2 is associated with increased zinc accumulation in human breast tumors (Courtesy of Dr. Veronica Lopez)