Disturbed expression of phase I and phase II estrogen-metabolizing enzymes in endometrial cancer: lower levels of CYP1B1 and increased expression of S-COMT.
Expression levels of genes encoding phase I and phase II estrogen-metabolizing enzymes: CYP1A1, CYP1A2, CYP1B1, CYP3A5, CYP3A7, SULT1A1, SULT1E1, SULT2B1, COMT, UGT2B7, and GSTP1 were studied by real-time PCR in 38 samples of cancerous and adjacent control endometrium. We found significantly lower levels of CYP1B1 and CYP3A7, higher levels of SULT2B1, UGT2B7 and GSTP1, and no differences in expression of COMT, CYP1A1, CYP3A5, SULT1E1 and SULT2A1 in the endometrial cancers. The CYP1B1 and COMT proteins were also examined by Western blotting and immunohistochemical staining, supporting the real-time PCR analysis. Lower levels of CYP1B1 detected in cancerous endometrium suggest its important role in control, precancerous tissue. Additionally, we showed for the first time higher protein levels of soluble COMT in cancerous endometrium, and higher levels of membrane-bound COMT in control, precancerous endometrium. The importance of the changed ratio between soluble and membrane-bound COMT still needs to be evaluated in further studies.
Hevir
Neli
N
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Sinkovec
Jasna
J
Rižner
Tea Lanišnik
TL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000201:enzymology / Q000473:pathology; D004958:Estradiol / Q000096:biosynthesis; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I / Q000235:genetics*; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D008875:Middle Aged; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism
D004967:Estrogens; D007527:Isoenzymes; D004958:Estradiol; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D015238:Sulfotransferases; C433248:SULT2B1 protein, human