Papilloma virus immortalized tracheal epithelial cells retain a well-differentiated phenotype.
Human airway epithelial cell lines that retain phenotypic properties representative of the native tissue will be useful physiological models. Human papilloma viral (HPV) genes can immortalize human genital keratinocytes and breast and bronchial epithelia. We transfected cystic fibrosis (CF) and normal tracheobronchial epithelial cell cultures with DNA encoding the HPV-18 E6 and E7 genes and characterized phenotypic properties of resultant cell lines. Of the 11 CF clones isolated, 6 developed a polarized phenotype with vectorial ion transport and membrane-specific expression of histamine and purinergic receptors. The ion transport properties of these lines differed from the normal lines and approximated those of primary CF airway epithelial cell cultures more closely than do those of cell lines transformed with the simian virus 40 large T gene. When transplanted into denuded tracheal grafts, these cells can differentiate into ciliated and secretory phenotypes. We conclude that HPV-18 E6 and E7 genes are sufficient to transform human airway epithelial cells and that the resultant cell lines express differentiated phenotypic properties that approximate those of the native epithelium.
Yankaskas
J R
JR
Division of Pulmonary Diseases, University of North Carolina, Chapel Hill 27599.
Haizlip
J E
JE
Conrad
M
M
Koval
D
D
Lazarowski
E
E
Paradiso
A M
AM
Rinehart
C A
CA
Sarkadi
B
B
Schlegel
R
R
Boucher
R C
RC
D000328:Adult; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels; D003550:Cystic Fibrosis / Q000473:pathology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000502:physiology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology; D009856:Oncogene Proteins, Viral / Q000032:analysis; D027383:Papillomaviridae / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea / Q000473:pathology / Q000503:physiopathology* / Q000637:transplantation; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002217:Carbachol; D001920:Bradykinin; D002118:Calcium