Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting 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 like other bZip family members e.g. Jun and Fos, ATF3 might play a role in the control of cell proliferation and participate in oncogenic transformation, To investigate this putative ATF3 function directly, the rat ATF3 protein was compared with v-Jun for its ability to transform primary cultures of chick embryo fibroblasts (CEFs). Like CEFs accumulating v-Jun, CEFs accumulating 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 cells could not promote colony formation from single cells in agar. Partial transformation induced by ATF3 was found to be associated with repression of multiple cellular genes that are also down-regulated by v-Jun, including those coding for the extracellular components fibronectin, decorin, thrombospondin 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 factor independence by down-regulating a subset of the genes repressed by v-Jun.