Immediate-Early Genes as Activity Markers in the CNS

Genetic analysis of viruses capable of producing tumors in mice led to the discovery of cancer-causing genes termed oncogenes. The v-fos oncogene is responsible for the ability of the FBJ-MSV virus to produce bone tumors (Finkel et al., 1966; Curran and Teich, 1982). Shortly after identification of v-fos , it became clear that this oncogene had a normal cellular counterpart (Curran et al., 1984). The normal cellular sequences from which the viral oncogene (v-fos ) was derived is referred to as thefos proto-oncogene or c-fos . The protein product of c-fos is a 55-kDa protein (Fos) that plays an important role in the signal transduction events mediating cell growth and division (Morgan and Curran, 1991), Proto-oncogenes such as c-fos contain negative regulatory elements that prevent overexpression (Sassone-Corsi et al., 1988; Gius et al,, 1990). However, these expression-limiting elements are not present within v-fos , enabling the FBJ-MSV virus to produce osteosarcomas (bone tumors). Overexpression of oncogene products in virally infected cells leads to tumor formation because the signal transduction pathways specifying growth and division become overstimulated (Carbone and Levme, 1990).