Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer.
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.
Department of Immunology, Tianjin Medical University, Heping District Qixiangtai Road No. 22, Tianjin 300070, People's Republic of China.
Hong Zhao
HZ
Li
Yue
Y
Wang
Yan
Y
Gao
Jie
J
Shao
Xiu Lan
XL
Zhao
Wei Min
WM
Deng
Yi Xin
YX
Liu
Jie
J
Yang
Zhi
Z
Yao
D000818:Animals; D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*
C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein