Abstract
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.
Highlights
It was demonstrated that Zn2+ is the ligand of the orphan receptor GPR39 [61], and we showed that it mediates metabotropic ZnR activity, which is termed ZnR/GPR39 [30,62]
ZnT2 was overexpressed in an ER+ breast cancer cell largely on ZnT2, whichvesicular has a well-described in the normal m line (T47D)focused where it appeared to enhance
A recent study reports that ZnR/GPR39 activation in breast cancer cells leads to activation of K+ /Cl- cotransporter KCC3, which may locally affect cell volume resulting in formation of protrusions [53]
Summary
A comprehensive analysis of the distribution of Zn2+ transporters in breast cancer tissue and cell lines revealed that transporter protein levels are aberrant [103]. ZnT2 was overexpressed in an ER+ breast cancer cell largely on ZnT2, whichvesicular has a well-described in the normal m line (T47D)focused where it appeared to enhance. MMP-2 activity, leading to a decrease in invasive properties of death, suggesting that, by accumulating Zn in vesicles/reducing the cytosolic cells [119]. When breast cancer tumor biopsies were studied, ZnT2 overexpressio in ZnT2, which are associated with low levels of Zn2+ secretion during lactation, are strated in luminal (ER+)subtypes. Changes in the ZnT2 expression pattern in breast cancer cells may provide a tumors, overexpression of ZnT2 increased vesicular Zn accumulation key to modulating Zn homeostasis in this tumor. It will be interesting to monitor whether the welltations in ZnT2, which are associated with low levels of Zn2+ secretion du are linked to specific breast cancer subtypes. Dimerization porters was suggested to provide anther pathway for their localization changes may affect expression patterns of other ZnT family members, and this should be carefully addressed
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