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

BMC Cancer. 2007 Aug 1:7:145. doi: 10.1186/1471-2407-7-145.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression*
  • Genes, jun*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary*
  • Mice
  • Mice, Nude
  • Phenotype
  • Transcription Factor AP-1 / metabolism
  • Transplantation, Heterologous

Substances

  • Transcription Factor AP-1