Zinc signaling in the mammary gland: For better and for worse

Zinc (Zn²⁺ ) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn²⁺ is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn²⁺ accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly, Zn²⁺ signaling also has direct roles in controlling mammary gland development or, alternatively, involution. During breast cancer progression, accumulation or redistribution of Zn²⁺ occurs in the mammary gland, with aberrant Zn²⁺ signaling observed in the malignant cells. Here, we review the current understanding of the role of in Zn²⁺ the mammary gland, and the proteins controlling cellular Zn²⁺ homeostasis and signaling, including Zn²⁺ transporters and the Gq-coupled Zn²⁺ sensing receptor, ZnR/GPR39. Significant advances in our understanding of Zn²⁺ signaling in the normal mammary gland as well as in the context of breast cancer provides new avenues for identification of specific targets for breast cancer therapy.