Research: Zinc Trafficking in the Mammary Gland
Mammary gland zinc transport and lactation
As the interface between the mother and newborn infant, the mammary gland provides
optimal post-natal nutrition through the secretion of milk which is a highly
complex biological fluid consisting of nutrients and non-nutritive factors such as cytokines,
hormones, and immunomodulatory cells. The mammary gland transfers abundant zinc into milk during
lactation. The dependence upon optimal zinc transfer is highlighted by the existence of a disorder
in humans referred to as "transient neonatal zinc deficiency" in which exclusively breastfed
infants can become severely zinc deficient. The specific cell-type within the mammary gland
responsible for the transport, production and secretion of milk components are the mammary
epithelial cells. Understanding the mechanisms through which the mammary gland regulates the
transfer of such copious amounts of zinc from maternal circulation, through the mammary gland and
into milk a central aim of our research.
The mammary gland is a very unusual exocrine gland in that once secretion is initiated, milk components are transported through the mammary gland in an episodic yet continual process over a long period of time. The initiation (lactogenesis), maintenance (galactopoeisis) and completion (involution) of lactation are regulated through complex hormonal signaling mechanisms, elicited primarily following the binding of prolactin to the prolactin receptor. We have previously determined that several zinc transporters integrate zinc transport in response to prolactin in mammary epithelial cells. Our long-term goal is to understand how expression and localization of these zinc transporters are regulated during lactation by hormonal signaling. Our laboratory explores the transcriptional, translational and post-translational mechanisms which are responsible for the regulation of zinc trafficking in the mammary epithelial cell to provide a better understanding of the role that maternal exposure to nutritional, environmental and hormonal factors play on the regulation of mammary gland function and nutrient transfer.
Mammary gland zinc transport and breast cancer
Breast cancer is the second leading cause of death in women. Approximately 270,000 women were diagnosed and ~ 41,000 are projected to die from breast cancer this year alone highlighting the urgent demand for validation and functional understanding of novel, predictive markers for breast cancer prognosis and therapy selection. Mounting evidence links dysregulated zinc transport with the transition and/or progression of breast cancer. This postulate is evidenced by aberrant expression of zinc transporting proteins in breast cancer biopsies from women or in cultured cell models that are responsible for maintaining zinc homeostasis. While these data illustrate the importance of tight regulation of zinc transport in mammary gland function, we still do not understand the relationship between breast cancer etiology and abnormal zinc transport regulation or aberrant cellular functions. 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.