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.
Subject(s)
Adenocarcinoma/genetics , Astrocytoma/genetics , Brain Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Meningioma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase/metabolism , Aldehyde Oxidase/genetics , Aldehyde Oxidase/metabolism , Astrocytoma/metabolism , Astrocytoma/pathology , Astrocytoma/surgery , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Child , Child, Preschool , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1B1/genetics , Cytochrome P-450 CYP1B1/metabolism , Female , Gene Expression Profiling , Glutathione S-Transferase pi/genetics , Glutathione S-Transferase pi/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Meningioma/metabolism , Meningioma/pathology , Meningioma/surgery , Metabolic Detoxication, Phase I/genetics , Metabolic Detoxication, Phase II/genetics , Middle AgedABSTRACT
Viewed in the plane of the cortical surface, the visual cortex is composed of overlapping functional maps that represent stimulus features such as edge orientation, direction of motion, and spatial frequency. Spatial relationships between these maps are thought to ensure that all combinations of stimulus features are represented uniformly across the visual field. Implicit in this view is the assumption that feature combinations are represented in the form of a place code such that a given pattern of activity uniquely signifies a specific combination of stimulus features. Here we review results of experiments that challenge the place code model for the representation of feature combinations. Rather than overlapping maps of stimulus features, we suggest that patterns of activity evoked by complex stimuli are best understood in the context of a single map of spatiotemporal energy.
