Abstract
Backgroundc-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells in vitro and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer in vivo is currently unknown.MethodsTo 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.ResultsEctopic 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.ConclusionThe 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.
Highlights
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 [1,2,3,4,5]
Effect of c-Jun expression on the proliferation and cell cycle of MCF-7 cells In order to investigate the effects of c-Jun on tumorigenesis and metastasis of breast cancer cells, pCDNA3.1/c-Jun was transfected into MCF-7 cells
Precise cell counts were obtained from samples of the cell suspensions by using a hemocytometer. 2 × 107 MCF-7 or MCF-7/c-Jun cells suspended in 200 μl of phosphate-buffered saline (PBS) were injected s.c. in the right flank
Summary
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 [1,2,3,4,5]. BMC Cancer 2007, 7:145 http://www.biomedcentral.com/1471-2407/7/145 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 Fra2) [6,7,8,9]. 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 [10,11,12,13]. The role of c-Jun on angiogenesis in rodents was described [23]
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