Reduced folate carrier: biochemistry and molecular biology of the normal and methotrexate-resistant cell.
The cytotoxic drug methotrexate uses the reduced folate carrier for transport into the cell, where it inhibits key enzymes in nucleotide biosynthesis. Resistance to methotrexate can be achieved by altering the genetic code of the reduced folate carrier gene and thus change the structure and function of the protein. Our understanding of RFC structure and function is based on the information gained from studying the uptake of folates and antifolates in living cells and the application of molecular techniques to determine gene expression and genetic mutations. The aim of this essay is to explain the structure and function of the reduced folate carrier, review the molecular biology of the reduced folate carrier gene and the mutations and polymorphisms that can result in methotrexate resistance.
Bosson
Geoffrey
G
School of Applied and Molecular Sciences, Ellison Building, Northumbria University, Newcastle-upon-Tyne NE1 8ST, UK. geoffrey.bosson@unn.ac.uk
D000595:Amino Acid Sequence; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D008727:Methotrexate / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D058978:Reduced Folate Carrier Protein
D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; D008727:Methotrexate