Characterization of vincristine-resistant HOB1 lymphoma cell line showing the classical MDR phenotype and altered expression of membrane glycoproteins.
A multidrug-resistant (MDR) cell line isolated from HOB1 lymphoma cells was characterized. The MDR phenotype in this cell line was typified by resistance to vincristine with varying degrees of cross-resistance to Adriamycin, colcemid and actinomycin D. Decreased intracellular [3H]vincristine with concurrent increase in the expression of a 170-kDa membrane glycoprotein (P-glycoprotein) suggested a plausible underlying mechanism for the development of resistance. Amplification of the mdr1 gene as well as a homogeneous staining region on the long arm of the 7th chromosome was observed. Moreover, metabolic studies with [14C]glucosamine or [14C]mannose indicated differential expressions of membrane glycoproteins between the drug-sensitive parental and drug-resistant descendant cells. It is concluded that the development of drug resistance in HOB1 lymphoma cells was strongly correlated with the overexpression of P-glycoprotein.
Lee
W P
WP
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Lee
C L
CL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D018076:DNA, Complementary; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008223:Lymphoma; D008358:Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010641:Phenotype; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism / Q000633:toxicity*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D014316:Tritium; D014750:Vincristine; D005947:Glucose; D008358:Mannose