In vitro effects of MYCN sense and antisense expression in MYCN-amplified human neuroblastoma cells.
Amplification of the MYCN oncogene is a strong predictor of treatment failure and chemo-resistance in childhood neuroblastoma. Stable expression of two partial MYCN gene fragments in antisense orientation reduced Mycn protein expression in an MYCN-amplified neuroblastoma tumor cell line, however, antisense cells did not exhibit an increased in vitro sensitivity to cytotoxic or differentiating agents. In contrast, partial MYCN sense transfectants exhibited increased resistance to cytotoxic drugs. These data suggest that the chemo-resistance of MYCN-amplified neuroblastoma cells is complex, and may be due to factors additional to Mycn protein expression.
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, Australia.
M
M
Kavallaris
M
M
Gardaneh
B
B
Cheung
M L
ML
Camacho
J E
JE
Hocker
M D
MD
Norris
M
M
Haber
G M
GM
Marshall
D000970:Antineoplastic Agents / Q000633:toxicity*; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D003001:Cloning, Molecular; D016373:DNA, Antisense; D004317:Doxorubicin / Q000633:toxicity; D005047:Etoposide / Q000633:toxicity; D005091:Exons; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007438:Introns; D009447:Neuroblastoma / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000633:toxicity
D000970:Antineoplastic Agents; D016373:DNA, Antisense; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D014212:Tretinoin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin