Characterization of Cyp2d22, a novel cytochrome P450 expressed in mouse mammary cells

Endogenous steroids and numerous environmental agents have potent effects o n mammary development and carcinogenesis. Locally produced cytochrome P450 enzymes that modify such molecules are therefore likely to be important reg ulators of these processes. Here we describe the characterization of a nove l mouse gene, termed Cyp2d22, that is highly expressed in the mammary tumor derived cell line RIIII/ Prl. Cyp2d22 is expressed at intermediate levels in the weakly tumorigenic cell line RIII/MG, whereas expression is low or a bsent in all normal mouse mammary epithelial cell lines tested and three C3 H mammary tumor derived cell lines. Immunoblot analysis of mouse tissues wi th highly specific antisera indicates that 2D22 protein levels are most abu ndant in liver, while intermediate levels of expression are seen in adrenal , ovary, and mammary gland. Immunohistochemical staining of liver sections with these antisera demonstrates that 2D22 is most abundant in the first la yer or two of parenchymal cells surrounding the central vein, with virtuall y no expression detected in periportal cells. Interestingly, sequence simil arity and functional data suggest that Cyp2d22 may be the mouse ortholog of human CYP2D6. These observations support the hypothesis that 2D22 mediates a distinct, biologically significant activity in relation to other mouse 2 D family members. (C) 2000 Academic Press.