Effects of Raf Kinase Inhibitor Protein Expression on Metastasis and Progression of Human Epithelial Ovarian Cancer
Open Access
- 1 June 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Research
- Vol. 6 (6), 917-928
- https://doi.org/10.1158/1541-7786.mcr-08-0093
Abstract
Loss of function of metastasis suppressor genes is an important step in the progression to a malignant tumor type. Studies in cell culture and animal models have suggested a role of Raf kinase inhibitor protein (RKIP) in suppressing the metastatic spread of prostate cancer, breast cancer, and melanoma cells. However, the function of RKIP in ovarian cancer (OVCA) has not been reported. To explore the potential role of RKIP in epithelial OVCA metastasis, we detected the expression levels of RKIP protein in tissue samples from patients with epithelial OVCA. Consequently, the expression of RKIP is reduced in the poorly differentiated OVCA than in the well-differentiated and moderately differentiated OVCA. In addition, in vitro cell invasion assay indicated that the RKIP expression was inversely associated with the invasiveness of five OVCA cell lines. Consistent with this result, the cell proliferation, anchorage-independent growth, cell adhesion, and invasion were decreased in RKIP overexpressed cells but increased in RKIP down-regulated cells. Further investigation indicated that RKIP inhibited OVCA cell proliferation by altering cell cycle progression rather than promoting apoptosis. Furthermore, the overexpression of RKIP suppressed the ability of human OVCA cells to metastasize when the tumor cells were transplanted into nude mice. Our data show the effect of RKIP on the proliferation, migration, or adhesion of OVCA cells. These results indicate that RKIP is also a metastasis suppressor gene of human epithelial OVCA. (Mol Cancer Res 2008;6(6):917–28)Keywords
This publication has 25 references indexed in Scilit:
- RKIP downregulates B-Raf kinase activity in melanoma cancer cellsOncogene, 2005
- The RAF proteins take centre stageNature Reviews Molecular Cell Biology, 2004
- Raf kinase inhibitory protein inhibits β-cell proliferationSurgery, 2004
- Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2Nature, 2003
- Metastasis suppressor pathways—an evolving paradigmCancer Letters, 2003
- Androgens and androgen receptor in prostate and ovarian malignanciesFrontiers in Bioscience-Landmark, 2003
- Allelotype Analysis of Common Epithelial Ovarian Cancers with Special Reference to Comparison between Clear Cell Adenocarcinoma with Other Histological TypesJapanese Journal of Cancer Research, 2002
- Ras/Raf signalling and emerging pharmacotherapeutic targetsExpert Opinion on Pharmacotherapy, 2002
- Raf Kinase Inhibitor Protein Interacts with NF-κB-Inducing Kinase and TAK1 and Inhibits NF-κB ActivationMolecular and Cellular Biology, 2001
- Human Phosphatidylethanolamine-binding Protein Facilitates Heterotrimeric G Protein-dependent SignalingJournal of Biological Chemistry, 2001