Background: Proto-oncogene c-Myc dysregulation is commonly found in aggressive tumors. Dysregulation is central to lymphomagenesis in Burkitt lymphoma and other non-Hodgkin's lymphomas. This suggests targeting c-Myc as a treatment for myc-associated malignancies. Methods: Microarrays showed c-Myc dysregulation in a B-lymphoblastoid line, TIB-215. This was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and extended to 3 additional Burkitt lymphoma lines. Growth effects of a c-Myc inhibitor, compound 10058-F4, were determined in these 4 lines using 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analyses and direct cell counts. Drug effects on c-Myc gene expression levels were measured using minor groove binding-TaqMan real-time reverse transcriptase-polymerase chain reaction. Drug specificity was analyzed in rat c-Myc knockout (-/-) and Myc-transfected cells. Results: c-Myc dysregulation was shown to be cell-cycle independent without rapid decay of c-Myc mRNA levels in all 4 lines. Using a c-Myc inhibitor, we found that growth inhibition was time- and dose-dependent. This inhibition caused unexpected downregulation (≥65%) of c-Myc mRNAs. Conclusions: The inhibition of c-Myc decreased growth in aggressive lymphoma cells. This mechanism included c-Myc mRNA downregulation and dissociation of c-Myc/Max protein heterodimer. These results support targeting c-Myc in tumors with high morbidity and mortality. © 2006 Elsevier Inc. All rights reserved.
CITATION STYLE
Gomez-Curet, I., Perkins, R. S., Bennett, R., Feidler, K. L., Dunn, S. P., & Krueger, L. J. (2006). c-Myc inhibition negatively impacts lymphoma growth. Journal of Pediatric Surgery, 41(1), 207–211. https://doi.org/10.1016/j.jpedsurg.2005.10.025
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