Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both in vitro and in nude mice.Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection.The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and in vivo liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy.The composite transcription factor activating protein-1 (AP-1) is thought to participate in fundamental cellular processes and control cellular responses to stimuli that regulate proliferation, differentiation, oncogenic transformation and apoptosis [1-5]. AP-1 proteins are composed principally of homodimers of Jun family members (c-Jun, JunB, JunD) or heterodimers of the Jun family members with the Fos family members (c-Fos, FosB, Fra-1, and Fra-2) [6-9]. These homodimers or heterodimers bind to specific DNA sequences, known as 12-Otetradecanoylphorbol-13-acetate response elements (TRE), in the promoter regions of target genes and activate transcription [10-13]. Among them, c-Jun is the major component of the AP-1 complex and c-Fos is its best-known partner. In vitro studies have demonstrated that Fos/Jun heterodimers are more stable and efficient in driving transcriptional activation than a Jun/Jun homodimer [14].c-Jun is frequently overexpressed in h