Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility.
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Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility. / Milde-Langosch, Karin; Janke, Stanislava; Wagner, Ines; Schröder, Christine; Streichert, Thomas; Bamberger, Ana Maria; Jänicke, Fritz; Löning, Thomas.
In: BREAST CANCER RES TR, Vol. 107, No. 3, 3, 2008, p. 337-347.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility.
AU - Milde-Langosch, Karin
AU - Janke, Stanislava
AU - Wagner, Ines
AU - Schröder, Christine
AU - Streichert, Thomas
AU - Bamberger, Ana Maria
AU - Jänicke, Fritz
AU - Löning, Thomas
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 107
SP - 337
EP - 347
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 3
M1 - 3
ER -
