Multidrug-resistant phenotype influences the differentiation of a human colon carcinoma cell line.
The human colon carcinoma cell line HT29-D4, which constitutively expresses a very low level of the MDR1 gene product, was made multidrug resistant by transfection with a human MDR1 cDNA from the pHaMDR1/A expression vector and selection by colchicine. Resistant clones were 3- to 15-fold resistant to colchicine and were cross-resistant to doxorubicin (3- to 4-fold). MDR1 gene expression was associated with the expression of functional P-glycoprotein (gp-170); the function was reversed by verapamil and cyclosporin A. HT29-D4 cells are able to differentiate in vitro by replacement of glucose by galactose in the culture medium and also to release the carcinoembryonic antigen (CEA). Under these culture conditions, MDR1 mRNA and gp-170 were always expressed and the protein remained functional. Upon galactose treatment, resistant clones were less differentiated since they showed a heterogeneous monolayer organization accompanied by heterogeneous staining of cell-surface CEA and a high decrease (60-90%) of CEA release.
Rimet
O
O
UPRESA-CNRS 6032, UFR Pharmacie, 27 Bd J. Moulin, Marseille, 13005, France.
Mirrione
A
A
Barra
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics*; D003078:Colchicine / Q000494:pharmacology; D003110:Colonic Neoplasms; D003470:Culture Media / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005690:Galactose / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D002272:Carcinoembryonic Antigen; D003470:Culture Media; D012333:RNA, Messenger; D004317:Doxorubicin; D005947:Glucose; D003078:Colchicine; D005690:Galactose