Expression of ATP-binding cassette transporter in human salivary ducts

Abstract P-glycoprotein expression has been observed in normal tissues as well as malignant tumours and thus does not appear to be induced by anticancer drugs. Knowledge of the distribution of ATP-binding cassette (ABC) transporters other than P-glycoprotein in normal salivary tissue is essential for understanding the physiological secretion or excretion of potentially toxic substances. Here the expression of ABC transporters was studied immunohistochemically in normal salivary gland tissue from nine patients. In striated duct cells, staining was strong for P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP 2/canalicular multispecific organic anion transporter (cMOAT), and lung resistance-related protein (LRP). The staining intensity of acinar and intercalated duct cells for MRP 1 expression was distinct from that for MRP2/cMOAT, but was similar to that for P-glycoprotein. LRP was observed as particles between the nuclear and luminal membranes in the cytoplasm of intercalated duct cells. The expression of ABC transporters suggests that numerous transporters other than those studied might be isolated from normal salivary tissues. These observations indicate that these ABC transporters may not arise from any previous contact with anticancer drugs but are expressed physiologically. The achieved drug resistance as well as the physiological secretory function of ABC transporters could contribute to the responsiveness to chemotherapy of malignant salivary tumours.