N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis

Abstract

The myc oncogenes are frequently activated in human tumors, but there is no comprehensive insight into the target genes and downstream cellular pathways of these transcription factors. We applied serial analysis of gene expression (SAGE) to identify targets of N‐myc in neuroblastomas. Analysis of 42 000 mRNA transcript tags in SAGE libraries of N‐myc‐ transfected and control neuroblastoma cells revealed 114 up‐regulated genes. The majority of these genes have a role in ribosome assembly and activity. Northern blot analysis confirmed up‐regulation of all tested transcripts. Induction was complete within 4 h after N‐myc expression. The large majority of the ribosomal proteins were induced, as well as genes controlling rRNA maturation. Cellular rRNA content was 45% induced. SAGE libraries and northern blot analysis confirmed up‐regulation of many of these genes in N‐myc‐amplified neuroblastomas. As N‐myc can functionally replace c‐myc, we analyzed whether N‐myc targets were induced by c‐myc as well. Approximately 40% of these N‐myc targets were up‐regulated in a c‐myc‐transfected melanoma cell line. These data suggest that myc genes function as major regulators of the protein synthesis machinery.

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

“…For example, MYC regulates ribosome biogenesis directly (34,35). PHF8 associates with hypomethylated rRNA genes and exerts a positive effect on rRNA transcription (36).…”

Myc pathways provoking cell suicide and cancer

“…Myc target genes have been identified by a number of approaches, most recently in SAGE and microarray screens designed to capture those targets induced or repressed following conditional activation of the oncoprotein (Coller et al, 2000;Boon et al, 2001;Neiman et al, 2001;Schuldiner and Benvenisty, 2001;Godfried et al, 2002;Iritani et al, 2002;Menssen and Hermeking, 2002;Watson et al, 2002;Yu et al, 2002;Ellwood-Yen et al, 2003;Huang et al, 2003). The cast of targets is ponderous (with at least 647 targets already identified, see http://www.myc-cancer-gene.org).…”

High delta‐like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type

“…SAGE libraries of 3 neuroblastoma tumours and 6 neuroblastoma cell lines with different genetic defects have been established in our laboratory. 23,24 In total 380,909 tags were sequenced from 9 neuroblastoma SAGE libraries. Since neuroblastoma is a childhood tumour, these SAGE libraries were analysed for expression of developmental control genes.…”