title: New proteins configure a brain drug resistance map in tuberous sclerosis.
abstract: Epileptogenic cortical tubers, characterized by dysplastic neurons and balloon cells, is a frequent feature of tuberous sclerosis. In severe tuberous sclerosis-affected individuals, seizures are refractory to medication. Multidrug resistance proteins (multidrug resistance protein-1 [MDR-1] and multidrug resistance-associated protein-1 [MRP-1]) have been found to be highly expressed in epileptogenic cortical tubers. However, two new proteins related to refractoriness in cancer (breast cancer resistance protein and major vault protein) have not been investigated in tuberous sclerosis and refractory epilepsy. On the same brain specimens previously describing the MDR-1 and MRP-1 expression, we investigated retrospectively breast cancer resistance protein and major vault protein by specific monoclonal antibodies and routine immunohistochemistry methods. Breast cancer resistance protein was present in vascular endothelial cells from all the vessels examined in 3 of 3 cases. Major vault protein was detected in only one case, and selectively expressed in several but not all ballooned cells. In epileptogenic cortical tubers, the additional expression of breast cancer resistance protein on vessels and major vault protein in some ballooned cells to the previously demonstrated expression of MDR-1 and MRP-1 (in vessels, astroglia, microglia, neurons, and ballooned cells) configures a brain protein pharmacoresistance map from patients with tuberous sclerosis and refractory epilepsy.
authors.affiliation: Clinical Biochemistry Department, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (UBA), Argentina. nadiatom@med.unc.edu
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Lazarowski
authors.forename: Fabiana J
authors.initials: FJ
authors.lastname: Lubieniecki
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Camarero
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Pomata
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Bartuluchi
authors.forename: Gustavo
authors.initials: G
authors.lastname: Sevlever
authors.forename: Ana Lía
authors.initials: AL
authors.lastname: Taratuto
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000150:complications / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1