FCE 24517-resistant MCF-7 human breast cancer cell line: selection and characterization.
We have developed a stable line of the human breast carcinoma cell line MCF-7 by in vitro continuous exposure to increasing concentrations of the antitumoral alkylating agent FCE 24517 (tallimustine). The selected line, MCF-7/24517(1), was resistant to the selecting agent (RI=10) and to a lesser degree to melphalan, MEN 10710 (a related dystamycin analog), doxorubicin and etoposide, but not to m-AMSA. MCF-7/24517(1) cells did not express the multidrug-resistant phenotype, evaluated in terms of mRNA for mdr-1 and gp170 glycoprotein. A significant, albeit modest, increase in the cellular content of glutathione was measured and therefore other resistance mechanism(s) should be operative. We conclude that the MCF-7/24517(1) line is a valuable model to investigate the mechanisms of resistance of FCE 24517 and its derivatives.
Salvatore
C
C
Pharmacology Department, Menarini Ricerche, Rome, Italy. menric@tin.it
Bigioni
M
M
Iafrate
E M
EM
Cianfriglia
M
M
Manzini
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004214:Distamycins / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000032:analysis; D006801:Humans; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004214:Distamycins; D009588:Nitrogen Mustard Compounds; D012333:RNA, Messenger; C066900:tallimustine; D005978:Glutathione