Studies of Secondary Transforming Events in Murine c-myc Retrovirus-Induced Monocyte Tumors
Rearrangement or deregulation of the c-myc gene has been observed in a variety of tumors and transformed cell lines (reviewed by Cole, 1986). Yet, the normal function or the exact contribution of c-myc in tumorigenesis remains controversial. We have recently described a tumor system in which a c-myc retrovirus induces monocyte/macrophage tumors in pristane treated BALB/c mice with very high frequency (Baumbach et al., 1986). This system has enabled us to begin dissecting the molecular changes during c-myc induced transformation of monocytes in vivo. Expression of c-myc alone is insufficient for full tumorigenicity, and as in the case of ras cooperativity (Land et al., 1983, Ruley et al., 1983), collaboration of a second genetic activation appears to be necessary. We have shown that in at least one monocyte tumor (tumor 7.1.3), a change involving the CSF-1 gene has occurred (Baumbach et al., 1987). In this tumor an endogenous ecotropic virus has integrated just upstream of the CSF-1 gene, thus activating production of CSF-1. This tumor now grows by an autocrine mechanism. Indeed all of the tumors have aquired a degree of autonomy, and so do not require CSF-1 for growth.
KeywordsLymphoma Kelly Plasmacytomas Pristane Cyclohexamide
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