Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility.
Fra-2 (Fos-related antigen 2) is a member of the Fos family of AP-1 transcription factors which is often up-regulated in mammary carcinomas. Previous results suggested that it might be involved in the regulation of breast cancer invasion and metastasis. In order to analyze the role of Fra-2 in breast cancer cells, it was silenced in the highly invasive MDA-MB231 cells using RNA interference. On the other hand, stable transfectants of the weakly invasive MCF7 cell line were established in order to analyze the effects of Fra-2 overexpression. In both approaches, cell proliferation was not or only weakly influenced by Fra-2. In contrast, the invasive potential of the cells was increased, and a weaker effect on motility was observed. By cDNA microarray analysis of the MCF7 transfectants followed by validation on a protein level, we identified several Fra-2 target genes which might be involved in cell invasion and migration, i.e., ALCAM and connexin 43. Additionally, mRNA expression levels of various genes which are associated with a more malignant behavior of the tumors in vivo were up- or downregulated, i.e., members of the MAGE family, S100P, TIMP2, IL24 etc. These results show that Fra-2 overexpression is associated with a more aggressive tumor phenotype and is probably involved in breast cancer progression in vivo.
Milde-Langosch
Karin
K
Clinic of Gynecology, University Clinics Hamburg-Eppendorf (UKE), Martinistr. 52, Hamburg 20246, Germany. milde@uke.uni-hamburg.de
Janke
Stanislava
S
Wagner
Ines
I
Schröder
Christine
C
Streichert
Thomas
T
Bamberger
Ana-Maria
AM
Jänicke
Fritz
F
Löning
Thomas
T
D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051921:Fos-Related Antigen-2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis
C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; D012333:RNA, Messenger