Disruption of the MYC transcriptional function by a small-molecule antagonist of MYC/MAX dimerization.
Inhibition of MYC/MAX dimerization by a small-molecule antagonist (IIA6B17) has been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, suggesting that the functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents. In the present study, a functional MYC reporter gene assay has been developed, using a luciferase gene construct under the control of the ornithine decarboxylase (ODC) gene promoter. This luciferase gene construct has been stably transfected into the MYCN amplified neuroblastoma cell line (NGP) and MYCC-overexpressed neuroepithelioma cell line (NB100). After exposure of the cell lines to IIA6B17 for 24 h, a significant reduction of luciferase activity was only observed in the NB100 cells, with IC50 values of approximately 28+/-9 microM, indicating that IIA6B17 has cell line-specific activity which may be selective for individual members of the MYC family.
Lu
Xiaohong
X
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Vogt
Peter K
PK
Boger
Dale L
DL
Lunec
John
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; D016271:Proto-Oncogene Proteins c-myc; D008156:Luciferases