Analysis of gene expression during myc oncogene-induced lymphomagenesis in the bursa of Fabricius

Abstract

The transcriptional effects of deregulated myc gene overexpression are implicated in tumorigenesis in a spectrum of experimental and naturally occurring neoplasms. In follicles of the chicken bursa of Fabricius, myc induction of B-cell neoplasia requires a target cell population present during early bursal development and progresses through preneoplastic transformed follicles to metastatic lymphomas. We developed a chicken immune system cDNA microarray to analyze broad changes in gene expression that occur during normal embryonic B-cell development and during mycinduced neoplastic transformation in the bursa. The number of mRNAs showing at least 3-fold change was greater during mycinduced lymphomagenesis than during normal development, and hierarchical cluster analysis of expression patterns revealed that levels of several hundred mRNAs varied in concert with levels of myc overexpression. A set of 41 mRNAs were most consistently elevated in myc-overexpressing preneoplastic and neoplastic cells, most involved in processes thought to be subject to regulation by Myc. The mRNAs for another cluster of genes were overexpressed in neoplasia independent of myc expression level, including a small subset with the expression signature of embryonic bursal lymphocytes. Overexpression of myc, and some of the genes overexpressed with myc, may be important for generation of preneoplastic transformed follicles. However, expression profiles of late metastatic tumors showed a large variation in concert with myc expression levels, and some showed minimal myc overexpression. Therefore, high-level myc overexpression may be more important in the early induction of these lymphomas than in maintenance of late-stage metastases.

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

“…WS5, a direct transcriptional target of Myc F Reiter et al be identified and analysed. This is a considerable challenge since key transcriptional regulators like Myc, involved in the control of many fundamental biological processes, affect the expression of many genes (Neiman et al, 2001;Menssen and Hermeking, 2002;Patel et al, 2004). However, not all of these genes are necessarily effectors of the biological functions of Myc (Grandori et al, 2000;Eisenman, 2001).…”

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).…”

Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation

“…Myc influences the transcription of a variety of target genes that could promote oncogenesis, including genes involved in cell growth and metabolism (Coller et al, 2000;Neiman et al, 2001). Myc has also been shown to increase vascular endothelial growth factor (VEGF) production in several cell types (Pelengaris et al, 1999;Baudino et al, 2002;Ruddell et al, 2003).…”