title: Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility.
abstract: 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.
authors: Clinic of Gynecology, University Clinics Hamburg-Eppendorf (UKE), Martinistr. 52, Hamburg 20246, Germany. milde@uke.uni-hamburg.de
authors: Karin
authors: K
authors: Milde-Langosch
authors: Stanislava
authors: S
authors: Janke
authors: Ines
authors: I
authors: Wagner
authors: Christine
authors: C
authors: Schröder
authors: Thomas
authors: T
authors: Streichert
authors: Ana-Maria
authors: AM
authors: Bamberger
authors: Fritz
authors: F
authors: Jänicke
authors: Thomas
authors: T
authors: Löning
mesh_terms: 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
chemical_list: C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; D012333:RNA, Messenger