The xenobiotic transporter, MRP2, in epithelia from insects, sharks, and the human breast: implications for health and disease.

A large number of mechanisms, including special excretory transporters, have evolved to help organisms excrete deleterious xenobiotics and endogenous molecules. We have examined the xenobiotic transport function of a putative multidrug resistance associated protein, MRP2, in three different epithelia: the insect renal (Malpighian) tubules, the secretory tubule of the shark rectal gland, and in ductules of the human breast. In the case of the insect and shark, transporter activity occurs in epithelia capable of great fluid transport. In the case of the insect Malpighian tubule, understanding the underlying mechanisms of this transporter may help with efforts to control populations of disease-carrying agriculturally important insects. In striking contrast, ductule architecture in nonlactating human breast ductules is that of an epithelium with a closed lumen. Immunocytochemical studies show that MRP2 is localized in the apical region of the ductule epithelial cells. In this unique case, MRP2 substrates transported into the lumen could possibly be concentrated. Transport substrates of MRP2 include carcinogens as well as antioxidants and other salutary molecules. Thus, in the breast ductule, MRP2 may play a significant role in breast epithelial cell health and cancer carcinogenesis.