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Characterization of Cytochrome P450 Enzymes in Human Breast Tissue from Reduction Mammaplasties¹

Department of Medical Nutrition (H.H., T.R., M.M., M.W., J.-Å.G.), Center for Nutrition and Toxicology (H.H., M.W.), and Department of Surgery (ER), Karolinska Institute at Huddinge University Hospital, Novum, S-141 86 Huddinge, Sweden

Cytochrome P450 (CYP) enzymes in the breast may have an important role in regulating the capacity of individual cells to metabolize hormones and environmental carcinogens. Very little is known about the P450 expression pattern in human breast because of the limited amount of accessible tissue and the difficulties associated with detection of low P450 levels. Breast tissue from reduction mammaplasties is the only tissue available in relative abundance. The correlation between the P450 content in this material and P450 in breast epithelium remains to be resolved. Also questionable is the value of RT-PCR detection of P450 forms in the breast without parallel detection of the protein. In this study, we have tried to determine whether the P450 profiles in reduction mammaplasty samples reflect those in the breast epithelium and whether P450 profiles on Western blots parallel RT-PCR detection. A comparison on the level of RT-PCR was made between P450 in 15 mammaplasty samples with that in 4 ductal carcinoma samples, and 1 dissected epithelial sample. The control epithelial sample contained CYP1A1, CYP1B1, CYP2A6, CYP2B6, CYP2E1, CYP2C, CYP3A, and CYP19 (aromatase). These forms were present also in the reduction samples, with CYP2E1 and CYP1B1 being detected in all samples. In addition, the reduction samples contained CYP4A11 and CYP2D6. CYP2B6, CYP2D6, and 2C were more easily detected in the carcinoma samples, thus differing from the reduction samples and the epithelial sample. CYP was isolated from the reduction samples, and the P450 profiles on Western blots were compared with the RT-PCR results. In general, there was good agreement between the two methods, and the discrepancies found were probably caused by lack of specific antibodies. We conclude that much useful information about P450 in the breast can be obtained from reduction mammaplasty samples.

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