Sequence and structural analysis of the presumed downstream promoter of the canine mdr1 gene

Abstract

The product of the canine mdr1 gene, P-glycoprotein (P-gp), plays an important role in chemotherapeutic drug resistance of several canine tumours. Increased expression of P-gp by tumour cells is associated with the multidrug-resistant phenotype. Because of its importance in cancer chemotherapy, a great deal is known about the regulation of mdr1 gene expression in human cancer patients and rodent cancer models. In contrast, there is no information regarding the regulation of P-gp expression in dogs. Initial information regarding the regulation of mdr1 gene expression can be gained by evaluating the mdr1 promoter. The downstream promoter of the canine mdr1 gene was sequenced. Several regulatory elements were identified, including an AP-1 site, AP-2 site and SP-1 site. The presumed canine mdr1 promoter was similar to that of other species; however, low overall sequence homology may suggest that aspects of P-gp regulation are distinctive in dogs.