Differential Expression of myc-family Genes During Development: Normal and Deregulated N-myc Expression in Transgenic Mice

Abstract

The myc-family of cellular oncogenes is a dispersed multi-gene family that includes the c-, N- and L-myc genes (For review see Alt et al., 1986). The human and murine c-, N, and L-myc genes encode related but distinct nuclear proteins and have a similar overall organization (Kohl et al., 1986; DePinho et al., 1986, Stanton et al., 1986; DePinho et al., 1987; Legouy et al., 1987; Kay et al., 1988); all have three exons with the first encoding a potentially untranslated leader sequence. All three genes also cooperate similarly with an activated Ha-Ras oncogene to transform primary rat embryo fibroblasts (REFs) (Yancopoulos et al., 1985; DePinho et al., 1987). Despite striking similarities of regions of the myc proteins and the in vitro transforming activities, the three genes are conserved as distinct sequences throughout vertebrate species suggesting unique functional roles. This possibility is supported by findings that the genes are differentially expressed in a stage-and tissue-specific manner during human and murine differentiation (Zimmerman et al., 1986). In addition, deregulated c-myc expression has been causally implicated in the genesis of a wide variety of different tumor types and occurs by a variety of different mechanisms; deregulation of the N- and L-myc genes has been clearly implicated only in a few naturally occurring tumors (eg. human neuroblastomas and small cell lung carcinomas) and only by the mechanism of gene amplification (reviewed by Alt et al., 1986).