The human onc gene c-myc: structure, expression, and amplification in the human promyelocytic leukemia cell line HL-60.

Abstract

Substantial evidence indicates that retroviral transforming (v-onc) genes originated by means of recombination between a present nontransforming virus and normal cellular sequences (Duesberg et al., this volume). These sequences, called cellular onc gene, are highly conserved during evolution, suggesting that they may code for protein products which are essential for cell growth or tissue differentiation. As these normal cellular genes are homologous to viral- transforming genes, their potential role in tumorigenesis is of great interest. As an alternative to direct transformation by a viral onc gene, abnormal activation of a cellular onc gene may cause transformation. Two models have been proposed for such a mechanism. First, high levels of expression of a cellular onc gene may be caused by the insertion nearby of a viral promoter [12, 15, 16, 17] or by alteration of the physiological promoter by a mutagenic agent such as a chemical carcinogen. Secondly, a cellular onc gene may be relocated in a transcriptionally active region of the genome as a consequence of chromosomal rearrangements [2, 5, 6, 13]. In this chapter we review the evidence for a possible third mechanism for onc gene activation in neoplastic cells, that of gene amplification. The human homologue, c-myc, of the transforming gene of avian myelocytomatosis virus (MC29), which is expressed at relatively high levels in the human promyelocytic leukemia cell line HL-60, is stably amplified in the genome of these cells [7]. Amplification was also detected in primary, uncultured leukemic cells from the same individual, suggesting that the c-myc amplification may have been involved in the leukemic transformation in this case.