Differential expression of myc family genes during murine development

Abstract

The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5′-noncoding exons, strikingly homologous coding regions^1–3, and display similar oncogenic potential in an in vitro transformation assay^4,5. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below), c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours⁷. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma^8–10, retinoblastoma^10,11 and small cell lung carcinoma (SCLC)¹². L-myc expression has so far been found only in SCLC⁶. Activated N-myc and L-myc expression has been implicated in oncogenesis^4–6,11,12; for example, although N-myc expression has been found in all neuroblastomas tested^9,10, activated (greatly increased) N-myc expression, resulting from gene amplification^8,13,14, is correlated with progression of the tumour¹⁵. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.