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

• Published in: PloS one 2015-11, Vol.10 (11), p.e0143285
• Main Authors: Stavrinou, Pantelis, Mavrogiorgou, Maria-Christina, Polyzoidis, Konstantinos, Kreft-Kerekes, Vincenzo, Timmer, Marco, Marselos, Marios, Pappas, Periklis
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - 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; Analysis; Astrocytoma; Astrocytoma - genetics; Astrocytoma - metabolism; Astrocytoma - pathology; Astrocytoma - surgery; Binding sites; Biomarkers; Brain; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - surgery; Brain tumors; Breast cancer; Cancer therapies; Carcinogens; Care and treatment; Central nervous system; Child; Child, Preschool; Complications and side effects; Correlation; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1B1 - genetics; Cytochrome P-450 CYP1B1 - metabolism; Cytochrome P450; Deactivation; Drug metabolism; Drug resistance; Enzymes; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - metabolism; Glutathione transferase; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; GSTT1 protein; Humans; Inactivation; Influence; Laboratories; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lungs; Male; Malignancy; Meningioma; Meningioma - genetics; Meningioma - metabolism; Meningioma - pathology; Meningioma - surgery; Metabolic Detoxication, Phase I - genetics; Metabolic Detoxication, Phase II - genetics; Metabolism; Metastases; Middle Aged; Neurosurgery; Oncology; Patients; Pharmacology; Physiological aspects; Prognosis; Protein expression; Proteins; Thermal cycling; Transcription; Tumors; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0143285

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. 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. 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. 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.