[MDR1 (ABCB1) gene encoding glycoprotein P (P-gp), a member of ABC transporter superfamily: consequences for therapy and progression of neoplastic diseases].
Glycoprotein P (P-gp) is a membrane protein belonging to the ABC transporter superfamily. As ATP-dependent pump it extrudes lipophilic particles out of the cell. P-gp was discovered in Chinese hamster ovary cells (CHO) where causing resistance to anticancer drugs. In a physiological state it is present in secretory organs and contribute to tissue barriers. P-gp transports wide variety of structurally diverse compounds including many anticancer drugs. Both environmental factors and mutations of the MDR1 gene may influence P-gp synthesis level. Linkage disequilibrium between single nucleotide polymorphisms (SNPs) of the MDR1 gene results from joint inheritance of these SNPs comprised in one haplotype. MDR1 polymorphism could affect the bioavailability of drugs which are P-gp substrates and thus influence the effectiveness of pharamacotherapy. Furthermore, P-gp protects organism against cancerogenic and toxic substances contained in the food and urine. A change in P-gp expression level or its activity is a putative cause of neoplastic disorders.
Panczyk
Mariusz
M
Molecular Biology and Pharmacogenomics Laboratory, Department of Pharmaceutical Biochemistry, Medical University of Lodz, 1 Muszyńskiego St., 90-151, Lodz, Poland. mario-pan@wp.pl
Sałagacka
Aleksandra
A
Mirowski
Marek
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents