Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis and reduces survival in a spontaneous xenograft model of human breast cancer

The effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA-MB-231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin deficient scid (select) mice. To identify Fra-2 target genes, we performed cDNA microarrays with mRNA isolated from xenograft tumour tissue. Fra-2 overexpression lead to a significantly shorter overall survival and a higher amount of spontaneous metastases in scid mouse lungs and compared to select mice indicating that Fra-2 regulates selectin binding sites on the tumour cell surface, which directly influence overall survival. By using cDNA microarray analysis of resected primary tumours a multitude of deregulated genes, which are known to be involved in metastasis formation The cells of two clones of MDA-MB231 line with Fra-2 overexpression (clone 1 and clone 2) as well as control cells were injected subcutaneously into scid mice and E- and P-selectin double knock-out scid mice (select). mRNA was isolated from xenograft tumour tissue (three tumours per group) and analyzed using Affimetrix transcriptome arrays.