title: Increased functional cell surface expression of CFTR and DeltaF508-CFTR by the anthracycline doxorubicin.
abstract: Cystic fibrosis (CF) is a disease that is caused by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, DeltaF508, accounts for 70% of all CF alleles and results in a protein that is defective in folding and trafficking to the cell surface. However, DeltaF508-CFTR is functional when properly localized. We report that a single, noncytotoxic dose of the anthracycline doxorubicin (Dox, 0.25 microM) significantly increased total cellular CFTR protein expression, cell surface CFTR protein expression, and CFTR-associated chloride secretion in cultured T84 epithelial cells. Dox treatment also increased DeltaF508-CFTR cell surface expression and DeltaF508-CFTR-associated chloride secretion in stably transfected Madin-Darby canine kidney cells. These results suggest that anthracycline analogs may be useful for the clinical treatment of CF.
authors: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3835, USA.
authors: R
authors: R
authors: Maitra
authors: C M
authors: CM
authors: Shaw
authors: B A
authors: BA
authors: Stanton
authors: J W
authors: JW
authors: Hamilton
mesh_terms: D000230:Adenocarcinoma; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D003110:Colonic Neoplasms; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007668:Kidney; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004317:Doxorubicin