title: Relative imbalances in the expression of catechol-O-methyltransferase and cytochrome P450 in breast cancer tissue and their association with breast carcinoma.
abstract: OBJECTIVE
  To investigate the expression levels of genes encoding phase I and phase II estradiol-metabolizing enzymes, and their association with breast cancer risk in Chinese women.
  
  
  METHODS
  The mRNA expression levels of cytochrome P450 (CYP) 1A1, 1B1 and 3A4 and catechol-O-methyltransferase (COMT) were examined in the breast tumor tissues, matched adjacent non-tumor tissues and the tissues with benign breast disease (BBD) by fluorescent quantitative real-time PCR.
  
  
  RESULTS
  Compared to BBD tissue, the mRNA expression of CYP1A1, CYP1B1 and CYP3A4 significantly reduced by 81.8%, 77.5%, and 85.6%, respectively, in the breast tumor tissue and by 27.2%, 38.8%, and 51.3%, respectively, in the adjacent non-tumor tissue in average (p<0.0001). COMT mRNA was 6.9 and 6.4 fold higher in the breast tumor and match non-tumor tissue (p<0.0001) than in the BBD, respectively. The level of COMT detected in pre-menopausal group and lymph nodal stage N1-N2 group was lower than that in post-menopausal group (p=0.0292) and N0 group (p=0.0389), respectively.
  
  
  CONCLUSIONS
  Significantly deceased expression of estradiol-metabolizing enzymes might result in the excess exposure of intratumoural E2, which could be one of the important risk factors for breast cancer. Significantly elevated COMT expression suggested that COMT could play a key role in breast tumor formation.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Xiao-Quan
authors.initials: XQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001941:Breast Diseases / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002681:China; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor; D002394:Catechol O-Methyltransferase; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D004958:Estradiol; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; C510163:CYP3A4 protein, human