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Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent
1Unité de Virologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM-U412), Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Abstract:
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.
Insights
Activating Transcription Factor 3 (ATF3) shows oncogenic potential in avian cells, partially transforming fibroblasts. ATF3 may induce growth factor independence by down-regulating specific genes, similar to v-Jun.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Activating Transcription Factor 3 (ATF3) is a transcription factor implicated in cell proliferation and oncogenic transformation.
- Previous studies in mammalian cells suggest ATF3's role in cancer, but direct investigation in avian systems was lacking.
Purpose of the Study:
- To directly compare the oncogenic potential of rat ATF3 with v-Jun in primary chick embryo fibroblasts (CEFs).
- To investigate the mechanism by which ATF3 might induce cellular transformation and growth factor independence.
Main Methods:
- Overexpression of rat ATF3 and v-Jun proteins in primary CEFs.
- Assessment of cellular morphology, growth in reduced serum conditions, and colony formation in agar.
- Analysis of gene expression changes, focusing on genes regulated by both ATF3 and v-Jun.
Main Results:
- CEFs overexpressing ATF3 exhibited altered morphology and enhanced growth in low-serum media, similar to v-Jun-transformed cells.
- ATF3-expressing cells did not form colonies in agar, indicating partial transformation compared to v-Jun.
- ATF3 repressed multiple cellular genes, including those for fibronectin, decorin, thrombospondin 2, and Par-4, many of which are also downregulated by v-Jun.
Conclusions:
- Rat ATF3 possesses intrinsic oncogenic potential in primary avian cells.
- ATF3 may induce growth factor independence by down-regulating a subset of genes also repressed by v-Jun.
- These findings highlight ATF3's role in cellular transformation and suggest a conserved mechanism of oncogenesis across species.