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Rahman M, Lax SF, Sutter CH, Tran QT, Stevens GL, Emmert GL, Russo J, Santen RJ, Sutter TR
CYP1B1 is not a major determinant of the disposition of aromatase inhibitors in epithelial cells of invasive ductal carcinoma
Drug Metabolism and Disposition (2008) 36:963-970.
Abstract
CYP1B1 and CYP19 ( aromatase) have been shown to be expressed in breast tumors. Both enzymes are efficient estrogen hydroxylases, indicating the potential for overlapping substrate and inhibitor specificity. We measured the inhibition properties of aromatase inhibitors (AIs) against CYP1B1-catalyzed hydroxylation of 17 beta-estradiol (E2) to determine whether CYP1B1 affects the disposition of AIs. In addition, we estimated the frequency of coexpression of these enzymes in breast tumor epithelium. Immunohistochemical analyses of CYP19 and CYP1B1 in a panel of 29 cases of invasive ductal carcinoma of the breast showed epithelial cell staining for CYP19 in 76% and for CYP1B1 in 97% of the samples. Statistical analysis showed no significant correlation (0.33) for positive expression of CYP19 and CYP1B1 ( p > 0.07). CYP1B1 inhibition was determined for two steroidal inhibitors: formestane and exemestane and five nonsteroidal inhibitors: aminoglutethimide, fadrozole, anastrozol!
Note
Publication Date: 2008-05-01.
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