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, and display similar oncogenic potential in an in vitro transformation assay. 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 tumours. 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, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. 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.

B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferation

“…Previous studies have shown that c-myc is ubiquitously expressed in developing tissues; however, in adult tissues, c-myc expression is more restricted and generally correlates with proliferation (Zimmerman et al, 1986;Ingvarsson et al, 1988a;Schmid et al, 1989;Semsei et al, 1989). In contrast, B-myc was previously found to be rather ubiquitously expressed in adult rat tissues based on a limited survey (Ingvarsson et al, 1988a).…”

Pattern of expression of c-erbB-2 oncoprotein in human fetuses

“…The widespread expression of the c-erbB-2 gene and its consistent presence in all three embryonic layers places it on a par with the myc (Zimmerman et al, 1986) and ras (Muller et al, 1982;Furth et al, 1987) families as a gene with a general role in fetal development. Other proto-oncogenes, such as c-ros (Neckameyer et al, 1986), c-src (Cotton & Brugge, 1983;Sorge et al, 1984;Neckameyer et al, 1986) and the int family (Jakobovits et al, 1986) appear to have a much more limited tissue distribution and may be involved in differentiated functions.…”

MYC oncogenes and human neoplastic disease

“…It has been known for some time that c-myc, N-myc and L-myc are expressed in distinct patterns during embryogenesis (Zimmerman et al, 1986;Zimmerman and Alt, 1990). c-myc tends to be highly expressed in most rapidly proliferating cells and is generally low to absent during quiescence.…”