Disturbed expression of phase I and phase II estrogen-metabolizing enzymes in endometrial cancer: lower levels of CYP1B1 and increased expression of S-COMT

Mol Cell Endocrinol. 2011 Jan 1;331(1):158-67. doi: 10.1016/j.mce.2010.09.011. Epub 2010 Sep 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Catechol O-Methyltransferase / genetics*
  • Cytochrome P-450 CYP1B1
  • Down-Regulation
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Endometrium / enzymology
  • Endometrium / pathology
  • Estradiol / biosynthesis
  • Estrogens / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Glutathione S-Transferase pi / genetics
  • Glutathione S-Transferase pi / metabolism
  • Humans
  • Hydroxylation
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Metabolic Detoxication, Phase I / genetics*
  • Metabolic Detoxication, Phase II / genetics*
  • Middle Aged
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism

Substances

  • Estrogens
  • Isoenzymes
  • Estradiol
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1
  • Catechol O-Methyltransferase
  • UGT2B7 protein, human
  • Glucuronosyltransferase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Sulfotransferases
  • SULT2B1 protein, human