Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany.
Department of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany.
Br J Cancer. 2014 Feb 4;110(3):753-63. doi: 10.1038/bjc.2013.774. Epub 2013 Dec 5.
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.
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.
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.
In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces.
C-Fos 最初被描述为癌基因，但与卵巢癌（OvCa）患者的良好预后相关。其产生这种作用的分子和功能方面尚不清楚。
使用 SKOV3 和 OVCAR8 细胞的稳定转染体，比较 c-FOS 过表达克隆和对照物的增殖、迁移、侵袭和凋亡潜能。在静态测定中分析对细胞外基质成分的黏附，在动态流动测定中分析对 E-选择素、内皮细胞和间皮细胞的黏附。通过将 SKOV3 克隆注入 SCID 小鼠的腹腔内研究 c-FOS 在体内的作用，并通过微阵列分析确定基因表达的变化。
c-FOS 过表达强烈延迟了注射到 SCID 小鼠后的肿瘤生长，减少了肺转移和循环肿瘤细胞。在体外，c-FOS 对增殖和迁移的影响较弱，但具有强烈的促凋亡作用。c-FOS 过表达的 OvCa 细胞对细胞外基质（胶原 I、IV）和 E-选择素、内皮细胞和间皮细胞的黏附显著降低。这与微阵列分析中黏附蛋白和糖基化酶的失调相对应。
除了已知的促凋亡作用外，c-FOS 还可能通过改变 OvCa 细胞对腹膜表面的黏附来影响 OvCa 的进展。
