This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kessler, R. Articles by Van Meir, E. G. Search for Related Content PubMed PubMed Citation Articles by Kessler, R. Articles by Van Meir, E. G.

Identification of the Putative Brain Tumor Antigen BF7/GE2 as the (De)Toxifying Enzyme Microsomal Epoxide Hydrolase¹

Laboratory of Tumor Biology and Genetics, Neurosurgery Department, University Hospital (CHUV), 1011 Lausanne, Switzerland [R. K., M-F. H., N. d. T., E. G. V. M.]; Laboratory of Molecular Neuro-Oncology, Neurosurgery Department and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322 [E. G. V. M.]; and Institute of Toxicology, University of Mainz, D-55131 Mainz, Germany [M. A.]

Malignant gliomas are the main cause of death from primary brain tumors. Despite surgery, radiation, and chemotherapy, patients have a median survival of less than a few years; therefore, it is clearly imperative to investigate new ways of treatment. The development of new therapeutic strategies for brain tumors is dependent on a better understanding of the differences between normal and tumoral brain cells. Our group had described previously a M_r 48,000 antigen defined by reactivity with two monoclonal antibodies (GE2 and BF7) obtained by immunization of mice with human glioblastoma cells.

Here, we describe the identification of the GE2/BF7 antigen as microsomal epoxide hydrolase (mEH), a drug-metabolizing enzyme that is involved both in toxification and detoxification of carcinogens. We initially used immunoaffinity purification using GE2 and BF7 and analyzed the purified proteins by microsequencing. Edman degradation identified 15 amino acids of the NH₂-terminal sequence that were 100% identical to mEH. To further confirm the identity of the BF7/GE2 antigen as mEH, we showed that the protein immunopurified with GE2 and BF7 was recognized by an anti-mEH antibody and that in vitro and in vivo synthesized human mEH is recognized by BF7 and GE2 antibodies. Furthermore, anti-mEH antibody recognizes an antigen expressed both in gliomas and reactive astrocytes, as do BF7 and GE2. Finally, we demonstrate that in contrast to what has been reported in rat embryo fibroblasts, p53 does not regulate mEH mRNA expression in glioma cells.

This article has been cited by other articles:

				R. S. Thomas, L. Pluta, L. Yang, and T. A. Halsey Application of Genomic Biomarkers to Predict Increased Lung Tumor Incidence in 2-Year Rodent Cancer Bioassays Toxicol. Sci., May 1, 2007; 97(1): 55 - 64. [Abstract] [Full Text] [PDF]

				B. Kaur, D. J. Brat, C. C. Calkins, and E. G. Van Meir Brain Angiogenesis Inhibitor 1 Is Differentially Expressed in Normal Brain and Glioblastoma Independently of p53 Expression Am. J. Pathol., January 1, 2003; 162(1): 19 - 27. [Abstract] [Full Text] [PDF]