Abstract
Abstract Abstract #2058 Background: Fra-1 and Fra-2 (Fos-related antigen1 and 2) are members of the Fos family of AP-1 transcription factors which are often up-regulated in human mammary carcinomas. The results of previous studies with clinical tumor tissues and experimental studies of breast cancer cell-lines suggested that they might be involved in the regulation of tumor invasion and metastasis in breast cancer.
 Materials and Methods: In order to analyze the impact of Fra-1 and Fra-2 on the aggressive behavior of breast cancer cells, we established stable transfectants of the weakly invasive MCF-7 cells and as well in the highly invasive MDA-MB231 breast cancer cells with Fra-1 and Fra-2 overexpression. Additionally we generated MCF-7 stable transfectants with inducible Fra-2 transcription controlled by the tetracycline-inducible tetON-system. The consequences of Fra-1 and Fra-2 upregulation on the biology of the breast cancer cells were analysed by MTT assays (proliferation) and Matrigel invasion assays (invasion and motility). In addition, possible target genes which were differentially regulated in stable transfectants with Fra-1 and Fra-2 overexpression were identified by microarray analysis and, partly Western blots.
 Results: Cell proliferation was not influenced by Fra-1 and Fra-2. In contrast, the invasive potential of the cells was increased by Fra-1 and Fra-2 in MDA-MB231 and MCF7 cells. In addition, there was a similar effect on cell motility. By using the GeneChip Human Genome U133A 2.0 array (Affymetrix), we identified several genes which are known to be involved in cell adhesion, migration or invasion and which were up- or downregulated in stable transfectants, i.e. ICAM, L1CAM, ALCAM, CX43 etc. Moreover, Fra-2 overexpression in MDA-MB231 cells resulted in CD44 upregulation and CD24 downregulation, which is characteristic of breast cancer stem cells.
 Discussion: In clinical breast cancer tissues, up-regulation of Fra-2 and Fra1 protein expression has been observed and was shown to be associated with a more aggressive phenotype. Our data of the experimental studies with breast cancer cell-lines indicates that Fra-2 as well as Fra-1 may play an important role in tumor progression by transcriptional regulation of genes which are involved in cell adhesion, invasion and motility. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2058.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
