title: Upregulation of breast cancer resistance protein and major vault protein in drug resistant epilepsy.
abstract: OBJECTIVE
  Identifying factors involved in the development of drug resistant epilepsy (DRE) remains a challenge. Candidate gene studies have shown modulation of resistance to drugs by various multidrug resistance proteins in DRE. However the resistance to drugs in DRE could be more complex and multifactorial involving molecules in different pharmacokinetic processes. In this study for the first time we have analyzed the relative expression of four molecules with different drug resistance mechanisms in two most common DRE pathologies, mesial temporal lobe epilepsy (MTLE) and focal cortical dysplasia (FCD) with respect to each other and also with different non-epileptic controls.
  
  
  METHODS
  Brain tissues resected from MTLE (n=16) and FCD type I and II (n=12) patients who had undergone surgery were analysed for mRNA levels of multidrug resistance-associated protein 1(MRP1), major vault protein (MVP), breast cancer resistance protein (BCRP), and one drug metabolising enzyme (UGT1A4) as compared to non-epileptic controls which were tissues resected from tumor periphery (n=6) and autopsy tissues (n=4) by quantitative PCR.
  
  
  RESULTS
  We found significant upregulation of MVP and BCRP whereas MRP1 and UGT1A4 were unaltered in both pathologies. While upregulation of BCRP was significantly higher in MTLE (9.34±0.45; p<0.05), upregulation of MVP was significantly higher in FCD (2.94±0.65; p<0.01).
  
  
  CONCLUSIONS
  We propose that upregulation of BCRP and MVP is associated with MTLE and FCD and these molecules not only may have the potential to predict pathology specific phenotypes but may also have therapeutic potential as adjunct treatment in these pathologies.
authors.affiliation: Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration, NBRC, Manesar, India. Electronic address: aparnabanerjeedixit@gmail.com.
authors.forename: Aparna
authors.initials: A
authors.lastname: Banerjee Dixit
authors.affiliation: Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration, NBRC, Manesar, India.
authors.forename: Devina
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Neurosurgery, AIIMS, New Delhi, India.
authors.forename: Arpna
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration, NBRC, Manesar, India.
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Banerjee
authors.affiliation: Department of Neurology, AIIMS, New Delhi, India.
authors.forename: Manjari
authors.initials: M
authors.lastname: Tripathi
authors.affiliation: Department of Forensic Medicine and Toxicology, AIIMS, New Delhi, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Prakash
authors.affiliation: Department of Neurosurgery, AIIMS, New Delhi, India. Electronic address: saratpchandra3@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Sarat Chandra
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000601:surgery; D001932:Brain Neoplasms / Q000378:metabolism / Q000601:surgery; D002648:Child; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D055815:Young Adult; D000099187:Major Vault Protein
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D014453:Glucuronosyltransferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C116614:ABCG2 protein, human; C019787:bilirubin glucuronoside glucuronosyltransferase; C421109:multidrug resistance-associated protein 1
keywords: BCRP; Drug resistant epilepsy; MVP; biotransformation enzyme; drug transporters