학술논문

c-FOS suppresses ovarian cancer progression by changing adhesion.
Document Type
Article
Source
British Journal of Cancer. 2/4/2014, Vol. 110 Issue 3, p753-763. 11p. 1 Color Photograph, 1 Chart, 4 Graphs.
Subject
*OVARIAN cancer
*CANCER invasiveness
*ONCOGENES
*GENE expression
*TUMOR growth
*CELL adhesion
*CANCER cell proliferation
*PROGNOSIS
Language
ISSN
0007-0920
Abstract
Background:C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown.Methods:Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis.Results:Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis.Conclusion:In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces. [ABSTRACT FROM AUTHOR]