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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Yan
Y
Institute of Basic Medical Sciences, Beijing, PR China. zhang_yan_2008@sina.com <zhang_yan_2008@sina.com>
Pu
Xiaoyun
X
Shi
Ming
M
Chen
Liyong
L
Song
Yuhua
Y
Qian
Lu
L
Yuan
Guogang
G
Zhang
Hao
H
Yu
Ming
M
Hu
Meiru
M
Shen
Beifen
B
Guo
Ning
N
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D016758:Genes, jun; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014183:Transplantation, Heterologous
D018808:Transcription Factor AP-1