Transcription factor ATF2 cooperates with v-Jun to promote growth factor-independent proliferation in vitro and tumor formation in vivo.

Abstract

ATF2 belongs to the bZIP family of transcription factors and controls gene expression via 8-bp ATF/CREB motifs either as a homodimer or as a heterodimer-for instance, with Jun-but has never been shown to be directly involved in oncogenesis. Experiments were designed to evaluate a possible role of ATF2 in oncogenesis in chick embryo fibroblasts (CEFs) in the presence or absence of v-Jun. We found that (i) forced expression of ATF2 cannot alone cause transformation, (ii) overexpression of ATF2 plus v-Jun specifically stimulates v-Jun-induced growth in medium with a reduced amount of serum, and (iii) the efficiency of low-serum growth correlates with the activity of a Jun-ATF2-dependent model promoter in stably transformed CEFs. Analysis of ATF2 and Jun dimerization mutants showed that the growth-stimulatory effect of ATF2 is likely to be mediated by v-Jun-ATF2 heterodimers since (i) v-Jun-m1, a mutant with enhanced affinity for ATF2, induces growth in low-serum medium much more efficiently than v-Jun, when expressed alone or in combination with ATF2; and (ii) ATF2/fos, a mutant that efficiently binds to v-Jun but is unable to form stable homodimers, shows enhanced oncogenic cooperation with v-Jun. In addition, we examined the role of ATF2 in tumor formation by subcutaneous injection of CEFs into chickens. In contrast to v-Jun, v-Jun-m1 gave rise to numerous fibrosarcomas while coexpression of ATF2 and v-Jun-m1 led to a dramatic development of fibrosarcomas visible within 1 week. Together these data demonstrate that overexpressed ATF2 potentiates the ability of v-Jun-transformed CEFs to grow in low-serum medium in vitro and contributes to the formation of tumors in vivo.

• Authors: S Huguier, J Baguet, S Perez, H van Dam, M Castellazzi
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 18 Issue 12 Pg. 7020-9 (Dec 1998) ISSN: 0270-7306 [Print] United States
• PMID: 9819389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Activating Transcription Factor 2
• Cyclic AMP Response Element-Binding Protein
• DNA-Binding Proteins
• Growth Substances
• Oncogene Protein p65(gag-jun)
• Oncogene Proteins
• Proto-Oncogene Proteins c-fos
• Recombinant Fusion Proteins
• Transcription Factors

Topics

• Activating Transcription Factor 2
• Animals
• Cell Division (genetics)
• Chick Embryo
• Cyclic AMP Response Element-Binding Protein (genetics)
• DNA-Binding Proteins (genetics)
• Gene Expression Regulation (genetics)
• Growth Substances (genetics)
• Leucine Zippers (physiology)
• Molecular Sequence Data
• Neoplasms, Experimental (genetics)
• Oncogene Protein p65(gag-jun) (genetics)
• Oncogene Proteins
• Proto-Oncogene Proteins c-fos (genetics)
• Recombinant Fusion Proteins (genetics)
• Transcription Factors (genetics)
• Transcriptional Activation (genetics)