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Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.

TitleExpression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.
Publication TypeJournal Article
Year of Publication2015
AuthorsStavrinou, P., Mavrogiorgou M-C., Polyzoidis K., Kreft-Kerekes V., Timmer M., Marselos M., & Pappas P.
JournalPLoS One
Volume10
Issue11
Paginatione0143285
Date Published2015
ISSN1932-6203
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.

DOI10.1371/journal.pone.0143285
Alternate JournalPLoS ONE
PubMed ID26580399
PubMed Central IDPMC4651330

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