title: ABCB1, ABCC1, and LRP gene expressions are altered by LDL, HDL, and serum deprivation in a human doxorubicin-resistant uterine sarcoma cell line.
abstract: Multidrug resistance (MDR) is the major cause of cancer treatment failure. The ATP-binding cassette-B1 (ABCB1) transporter, also known as MDR1 or P-glycoprotein, is thought to promote the efflux of drugs from cells. MDR is also associated with the multidrug resistance-associated protein 1 (ABCC1) and the lung resistance-related protein (LRP), a human major vault protein. Moreover, MDR has a complex relationship with lipids. The ABCB1 has been reported to modulate cellular cholesterol homeostasis. Conversely, cholesterol has been reported to modulate multidrug transporters. However, results reported to date are contradictory and confusing. The aim of this study was to investigate whether LDL, HDL, and serum deprivation could influence ABCB1, ABCC1, and LRP expression in a human doxorubicin-resistant uterine sarcoma cell line. ABCB1 and ABCC1 expression increased after 24 h of serum deprivation, and expression returned to basal levels after 72 h. LDL, depending on concentration, increased ABCB1, ABCC1, and LRP expression. ABCB1 expression increased at low HDL, and decreased at high HDL concentrations. We demonstrated that serum deprivation and lipoproteins, particularly LDL, modulated ABCB1 expression and, to a lesser extent, ABCC1 expression. This finding may link the phenomena of drug transport, cholesterol metabolism and cancer.
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, Room 43, 05403-000 São Paulo, SP, Brazil. Electronic address: deiaturb@bol.com.br.
authors.forename: Andréa Turbuck
authors.initials: AT
authors.lastname: Celestino
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, Room 43, 05403-000 São Paulo, SP, Brazil. Electronic address: deb.levy@lim31.fm.usp.br.
authors.forename: Débora
authors.initials: D
authors.lastname: Levy
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, Room 43, 05403-000 São Paulo, SP, Brazil. Electronic address: jorgeruiz@usp.br.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Maria Ruiz
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, Av.Dr.Enéas de Carvalho Aguiar, 155, 1st floor, Room 43, 05403-000 São Paulo, SP, Brazil. Electronic address: spbydlow@usp.br.
authors.forename: Sérgio Paulo
authors.initials: SP
authors.lastname: Bydlowski
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABCB1; ABCC1; LRP; Lipoproteins; Multiple drug resistance