Induction of Hematopoietic Tumors Using a Viral Construct Containing c-myc cDNA from Normal Mouse Spleen

Abstract

Deregulated expression of the c-myc protooncogene is assumed to be a major contributing factor to the development of plasmacytomas in pristane-primed BALB/c mice (reviewed in Potter, 1986) and murine T cell lymphomas induced by AKR and Moloney murine leukemia viruses (MuLV) (Steffen 1984, Selden et al. 1984, Li et al. 1 984, Corcoran et al. 1984). Studies on the c-myc expression in plasmacytomas suggest that myc can be deregulated by a variety of mechanisms. These include stabilization of the myc message due to an altered transcriptional unit (Piechaczyk et a1. 1985), removal of cis-acting regulatory sequences (Yang et al. 1985) and augmentation of transcriptional activity resulting from apposed IgH enhancer sequences (Corcoran, 1985). These studies provide substantial inferential support for the view that aberrant expression of myc is central to the trarisformation of murine plasma cells and T cells but direct evidence to buttress this argument has been lacking. Efforts to develop this evidence have taken several complementary directions, all resulting in abnormally high levels of myc expression in somatic cells. These include the development of transgenic mice with murine or human c-myc genes driven by selected promoter/enhancer sequences (Stewart et al. 1 984; Adams et al. 1986) or infection of mice with recombinant murine retroviruses containing avian v-myc genes (Morse et al. 1986; Potter et al. 1986). The avian v-myc genes are known to contain numerous coding region mutations in comparison to normal avian c-myc sequences and also differ from normal murine c-myc genes (Papas and Lautenberger 1985). Since sequence differences among avian v-myc genes appear to contribute to variations in their oncogenic potentials (Enrietto et al. 1984), we wished to determine if overexpression of a normal murine c-myc gene in mice would result in the development of tumors. This report describes the features of two new recombinant murine retroviruses containing normal mouse c-myc coding sequences and the results obtained when pseudotypes of these viruses were used to infect adult, pristane-primed BALB/c mice.