title: Major vault protein, a marker of drug resistance, is upregulated in refractory epilepsy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, England. sisodiya@ion.ucl.ac.uk
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
authors.forename: Lillian
authors.initials: L
authors.lastname: Martinian
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Brian N
authors.initials: BN
authors.lastname: Harding
authors.forename: Maria
authors.initials: M
authors.lastname: Thom
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009363:Neoplasm Proteins / Q000235:genetics; D018302:Neoplasms, Neuroepithelial / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D012016:Reference Values; D012598:Sclerosis; D015854:Up-Regulation / Q000235:genetics; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000927:Anticonvulsants; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C116614:ABCG2 protein, human