Establishment and characterization of a cisplatin-resistant human neuroblastoma cell line.
BACKGROUND
To investigate the mechanisms of cisplatin (CDDP)-resistance in neuroblastoma(NB), we established a CDDP-resistant human NB cell line, BM1R2.


METHODS
We characterized BM1R2 in terms of the susceptibilities to other anticancer agents, MDR1 and MRP expression, MYCN amplification, intracellular gultathione-S-transferase(GST-pi), metallothionein(MT) and gultathione(GSH) levels, and immunocytochemical and cytogenetic features.


RESULTS
When compared to parent BM1 line, BM1R2 exhibited a 17.0-fold resistance to CDDP and cross-resistance to other agents. MRP expression was only observed in BM1R2, whereas MDR1 was expressed in both lines. Notably higher intracellular GST-pi and MT levels were observed in BM1R2 cells. MYCN amplifications were 50 and 6 copies in BM1 and BM1R2, respectively, and additional aberrations were observed in chromosome 1 and 2 in BM1R2.


CONCLUSIONS
It was suggested that GST-pi and MT could exert crucial roles on CDDP-resistance in our system. BM1R2 is of great interest for investigating the mechanisms of CDDP-resistance in NB.
Yasuno
T
T
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Matsumura
T
T
Shikata
T
T
Inazawa
J
J
Sakabe
T
T
Tsuchida
S
S
Takahata
T
T
Miyairi
S
S
Naganuma
A
A
Sawada
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000494:pharmacology*; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D008668:Metallothionein / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002945:Cisplatin; D005978:Glutathione; D005982:Glutathione Transferase; D008668:Metallothionein; D027425:ATP-Binding Cassette, Sub-Family C Proteins