title: Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.
abstract: BACKGROUND
  Endogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3) and some of their proteins.
  
  
  METHODS
  Using qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary.
  
  
  RESULTS
  Meningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas.
  
  
  CONCLUSIONS
  The various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself.
authors.affiliation: Department of Neurosurgery, University of Cologne, Cologne, Germany.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Stavrinou
authors.affiliation: Laboratory of Pharmacology, University of Ioannina, Ioannina, Greece.
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Mavrogiorgou
authors.affiliation: Department of Neurosurgery, AHEPA University Hospital, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Polyzoidis
authors.affiliation: Department of Neurosurgery, University of Cologne, Cologne, Germany.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Kreft-Kerekes
authors.affiliation: Department of Neurosurgery, University of Cologne, Cologne, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Timmer
authors.affiliation: Laboratory of Pharmacology, University of Ioannina, Ioannina, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Marselos
authors.affiliation: Laboratory of Pharmacology, University of Ioannina, Ioannina, Greece.
authors.forename: Periklis
authors.initials: P
authors.lastname: Pappas
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D042931:Aldehyde Oxidase / Q000235:genetics / Q000378:metabolism; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D008875:Middle Aged
chemical_list: C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase; C526436:AOX1 protein, human; D042931:Aldehyde Oxidase; C413545:glutathione S-transferase T1; C483009:GSTM3 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase