Transcription factor ATF3 partially transforms chick embryo fibroblasts bypromoting growth factor-independent proliferation

Activating Transcription Factor 3 (ATF3) is a member of the bZip family of transcription factors. Previous studies in mammalian cells suggested that l ike other bZip family members e.g. Jun and Fos, ATF3 might play a role in t he control of cell proliferation and participate in oncogenic transformatio n, To investigate this putative ATF3 function directly, the rat ATF3 protei n was compared with v-Jun for its ability to transform primary cultures of chick embryo fibroblasts (CEFs). Like CEFs accumulating v-Jun, CEFs accumul ating the ATF3 protein displayed a typical, fusiform morphology, associated with an enhanced capacity to grow in medium with reduced amount of serum. However, in contrast to v-Jun-transformed CEFs, the ATF3 overexpressing cel ls could not promote colony formation from single cells in agar. Partial tr ansformation induced by ATF3 was found to be associated with repression of multiple cellular genes that are also down-regulated by v-Jun, including th ose coding for the extracellular components fibronectin, decorin, thrombosp ondin 2, and the pro-apoptotic protein Par-4. These data demonstrate that, at least in primary avian cells, rat ATF3 possesses an intrinsic oncogenic potential. Moreover, the results suggest that ATF3 might induce growth fact or independence by down-regulating a subset of the genes repressed by v-Jun .