Isolation and characterization of an adriamycin-resistant breast tumor cell line.
An adriamycin-resistant human breast tumor cell line MDA-A1R was generated by step-wise selection in increasing concentrations of drug from the parent cell line MDA-MB-231. MDA-A1R cells grow as loosely attached cell aggregates with a doubling time of 28-32 h; the MDA-MB-231 parent cell line grows as a standard monolayer culture with a 20-h doubling time. The MDA-A1R cell line is highly resistant to adriamycin compared to the parent cell line, and is cross-resistant to velban and colchicine suggestive of a multidrug resistance (MDR) phenotype. MDA-A1R cells exhibit reduced net adriamycin content as compared to the parent cell line. The MDR-associated P-glycoprotein gene is amplified approximately 10- to 30-fold in MDA-A1R cells. P-glycoprotein sequences are overexpressed in the resistant cells and are stable for up to 13 wk after drug removal. Moreover, MDA-A1R cells show the presence of very high levels of P-glycoprotein. MDA-A1R is thus an in vitro model system to study the mechanism of MDR in human breast cancer.
Schneider
S L
SL
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Fuqua
S A
SA
Speeg
K V
KV
Tandon
A K
AK
McGuire
W L
WL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma; D015139:Blotting, Southern; D001943:Breast Neoplasms; D002449:Cell Aggregation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D046508:Culture Techniques / Q000379:methods; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D014747:Vinblastine; D004317:Doxorubicin; D003078:Colchicine