title: Characterization of Cyp2d22, a novel cytochrome P450 expressed in mouse mammary cells.
abstract: Endogenous steroids and numerous environmental agents have potent effects on mammary development and carcinogenesis. Locally produced cytochrome P450 enzymes that modify such molecules are therefore likely to be important regulators of these processes. Here we describe the characterization of a novel mouse gene, termed Cyp2d22, that is highly expressed in the mammary tumor derived cell line RIII/Prl. Cyp2d22 is expressed at intermediate levels in the weakly tumorigenic cell line RIII/MG, whereas expression is low or absent in all normal mouse mammary epithelial cell lines tested and three C3H mammary tumor derived cell lines. Immunoblot analysis of mouse tissues with highly specific antisera indicates that 2D22 protein levels are most abundant 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 layer or two of parenchymal cells surrounding the central vein, with virtually no expression detected in periportal cells. Interestingly, sequence similarity 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 2D family members.
authors.affiliation: Strang Cancer Research Laboratory, New York, New York 10021, USA.
authors.forename: N
authors.initials: N
authors.lastname: Blume
authors.forename: J
authors.initials: J
authors.lastname: Leonard
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Xu
authors.forename: O
authors.initials: O
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Remotti
authors.forename: J
authors.initials: J
authors.lastname: Fishman
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D002460:Cell Line; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D008321:Mammary Glands, Animal / Q000201:enzymology*; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; C414739:Cyp2d22 protein, mouse; D019389:Cytochrome P-450 CYP2D6; D000072467:Cytochrome P450 Family 2