Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes.
To investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF-10A, negative for the expression of the P-glycoprotein, with c-Ha-ras and/or c-erbB-2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr-1 mRNA expression, the presence of P-glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF-10A transfected with both c-Ha-ras and c-erbB-2 oncogenes acquired the MDR phenotype.
Sabbatini
A R
AR
Haematology Unit, University of Pisa, Italy.
Basolo
F
F
Valentini
P
P
Mattii
L
L
Calvo
S
S
Fiore
L
L
Ciardiello
F
F
Petrini
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010641:Phenotype; D014162:Transfection; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D014700:Verapamil