Induction of Bone Tumors in Transgenic Mice by C-FOS Depends on the Presence of a Retroviral Long Terminal Repeat

Expression of the protooncogene C-FOS can lead to the development of bone tumors in transgenic mice. However, recent experiments have suggested that the tumor induction is independent of the promoter chosen for the C-FOS expression construct but dependent on modifications in the 3′ untranslated region (3′UTR) of the C-FOS gene. To investigate this effect, C-FOS expression constructs have been tested in transgenic mice for their ability to induce bone tumors. Removal of 3′UTR sequences known to affect the stability of C-FOS mRNA resulted in high expression in several organs but gave no detectable bone lesions. In contrast, the presence of different long terminal repeats of murine retroviruses at the 3′UTR caused the induction of bone tumors. These data suggest that the C-FOS gene can be converted into a tumor-inducing oncogene only by retroviral control elements.