Gene expression of 17beta-estradiol-metabolizing isozymes: comparison of normal human mammary gland to normal human liver and to cultured human breast adenocarcinoma cells.

Abstract

Metabolic activation of 17beta-estradiol (E2) to catechols and quinones together with lack of deactivation constitute risk factors in human breast carcinogenesis. E2-catchols are generated by cytochrome P450-dependent monooxygenases (CYPs). Deactivation of E2, E2-catechols, and E2-quinones is mediated by UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), catechol-O-methyltransferase (COMT), glutathione-S-transferase (GST), and NADPH-quinone-oxidoreductase (QR) isozymes, respectively. The aim of the present study was to quantify mRNA levels of E2-metabolizing isozymes expressed in MCF-7 cells cultured in the presence/absence of steroids by reverse transcription/competitive PCR in relation to the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase and compare them with expression levels in normal human mammary gland (MG) and liver tissue. CYP1A1, 1B1, SULT1A1, 1A2, membrane-bound and soluble COMT, GSTT1, QR1, and UGT2B7 were detected in both tissues and MCF-7 cells; however, most enzymes were expressed at least tenfold higher in liver. Yet, CYP1B1 was expressed as high in breast as in liver and UGTs were not detected in MCF-7 cells cultured with steroids. MCF-7 cells cultured steroid-free additionally expressed CYP1A2 as well as UGT1A4, 1A8, and 1A9. Normal human liver but not MG expressed CYP1A2, 3A4, UGT1A1, 1A3, 1A4, 1A9, and SULT2A1. UGT1A8 was only detected in MCF7 cells but was not found in human liver. Thus, our study provides a comprehensive overview of expression levels of E2-metabolizing enzymes in a popular in vitro model and in human tissues, which will contribute to the interpretation of in vitro studies concerning the activation/deactivation of E2.

• Authors: Leane Lehmann, Jörg Wagner
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 617 Pg. 617-24 ( 2008) ISSN: 0065-2598 [Print] United States
• PMID: 18497089 (Publication Type: Journal Article)

Chemical References

• Estrogens
• Estrogens, Catechol
• RNA, Messenger
• Estradiol
• Cytochrome P-450 Enzyme System
• Catechol O-Methyltransferase
• UGT1A1 enzyme
• Glucuronosyltransferase
• UDP-glucuronosyltransferase, UGT1A8
• Glutathione Transferase

Topics

• Adenocarcinoma (enzymology, genetics)
• Breast (enzymology)
• Breast Neoplasms (enzymology, genetics)
• Catechol O-Methyltransferase (genetics, metabolism)
• Cells, Cultured
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• Estradiol (pharmacology)
• Estrogens (pharmacology)
• Estrogens, Catechol (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glucuronosyltransferase (genetics, metabolism)
• Glutathione Transferase (genetics, metabolism)
• Humans
• Liver (enzymology)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction