Universität zu Köln

Stavrinou, Pantelis ORCID: 0000-0001-8653-1395, Mavrogiorgou, Maria-Christina, Polyzoidis, Konstantinos, Kreft-Kerekes, Vincenzo, Timmer, Marco, Marselos, Marios and Pappas, Periklis (2015). Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors. PLoS One, 10 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stavrinou, Pantelis UNSPECIFIED orcid.org/0000-0001-8653-1395 UNSPECIFIED Mavrogiorgou, Maria-Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Polyzoidis, Konstantinos UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreft-Kerekes, Vincenzo UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmer, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Marselos, Marios UNSPECIFIED UNSPECIFIED UNSPECIFIED Pappas, Periklis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-386890
DOI:	10.1371/journal.pone.0143285
Journal or Publication Title:	PLoS One
Volume:	10
Number:	11
Date:	2015
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLUTATHIONE S-TRANSFERASES; RODENT GLIOMA MODEL; PHASE-II TRIAL; CYTOCHROME-P450 EXPRESSION; ALDEHYDE DEHYDROGENASES; PLUS O-6-BENZYLGUANINE; LUNG-CANCER; ENZYMES; TEMOZOLOMIDE; RISK Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38689