Transcriptional Amplification in Tumor Cells with Elevated c-Myc
Menée sur un modèle murin, cette étude met en évidence un mécanisme par lequel, en amplifiant la transcription de certains gènes, le facteur c-Myc favorise la croissance des cellules tumorales
Elevated expression of the c-Myc transcription factor occurs frequently in human cancers and is associated with tumor aggression and poor clinical outcome. The effect of high levels of c-Myc on global gene regulation is poorly understood but is widely thought to involve newly activated or repressed Myc target genes. We report here that in tumor cells expressing high levels of c-Myc the transcription factor accumulates in the promoter regions of active genes and causes transcriptional amplification, producing increased levels of transcripts within the cell s gene expression program. Thus, rather than binding and regulating a new set of genes, c-Myc amplifies the output of the existing gene expression program. These results provide an explanation for the diverse effects of oncogenic c-Myc on gene expression in different tumor cells and suggest that transcriptional amplification reduces rate-limiting constraints for tumor cell growth and proliferation. º Oncogenic c-Myc occupies promoters of most active genes in tumor cells º Oncogenic c-Myc increases RNA levels within cell s existing gene expression program º Oncogenic c-Myc is an amplifier, not a specifier, of gene expression in cancer cells Myc-induced transcriptional amplification, rather than the switching on of Myc target genes is important for tumorigenesis, suggesting that therapies targeting the apparatus involved in transcriptional amplification may be useful in the treatment of cancer.
Cell , résumé, 2011