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Major Vault Protein, a Marker of Drug Resistance, Is Upregulated in Refractory Epilepsy
Author(s) -
Sisodiya Sanjay M.,
Martinian Lillian,
Scheffer George L.,
Valk Paul van der,
Cross J. Helen,
Scheper Rik J.,
Harding Brian N.,
Thom Maria
Publication year - 2003
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2003.21803.x
Subject(s) - downregulation and upregulation , abcg2 , cortical dysplasia , epilepsy , drug resistance , pathology , medicine , biology , cancer research , neuroscience , transporter , atp binding cassette transporter , biochemistry , gene , microbiology and biotechnology
Summary: Purpose: The molecular basis of drug resistance in epilepsy is being explored. Two proteins associated with drug resistance in cancer, P‐glycoprotein and multidrug resistance–associated protein 1, are upregulated in human epileptogenic pathologies. Other proteins associated with resistance in cancer include major vault protein (MVP) and breast cancer resistance protein (BCRP). We hypothesized that these proteins would also be upregulated in human epileptogenic pathologies. Methods: Hippocampal sclerosis (HS), focal cortical dysplasia (FCD), and dysembryoplastic neuroepithelial tumor (DNT) were studied by using immunohistochemistry for MVP and BCRP. Nonepileptogenic control and histologically normal brain adjacent to epileptogenic tissue were used for comparison. Results: MVP and BCRP were expressed ubiquitously in brain capillary endothelium. Ectopic upregulation of MVP was seen in hilar neurons in HS, dysplastic neurons in FCD, and lesional neurons in DNT. Only in HS cases were rare extralesional neurons immunoreactive. Glial upregulation was not seen. There was no qualitative upregulation of BCRP. Conclusions: These results show that more than one resistance protein may be upregulated in a given epileptogenic pathology and may contribute to drug resistance. Determination of the types, amounts, and distribution of such proteins will be necessary for rational treatment for drug resistance in epilepsy.