Dkk-3 Induces Apoptosis Through Mitochondrial and Fas Death Receptor Pathways in Human Mucinous Ovarian Cancer Cells
説明
Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in human cancers. Dkk-3 possesses an antiproliferative activity and induces apoptosis in tumor cells, suggesting that it functions as a tumor suppressor. In this study, we investigated the molecular function of Dkk-3 in human ovarian cancer cells.We assessed the levels of Dkk-3 protein expression in human mucinous and clear cell ovarian cancer cells, and compared cell viabilities between cell lines that expressed Dkk-3 and those that did not, as well as between cells that expressed Dkk-3 and those whose expression of Dkk-3 was reduced by small interfering RNA. We also evaluated the characteristic fragmentation of DNA to detect apoptosis in Dkk-3-deficient cells. To further investigate the molecular mechanisms of apoptosis, we assessed the expression of molecules involved in apoptosis signaling pathways in Dkk-3-deficient cells.The expression of the Dkk-3 protein was observed in most of the ovarian cancer cell lines tested. Dkk-3-deficient cells showed faster growth than Dkk-3-replete cells. The characteristic fragmentation of DNA was not observed in Dkk-3-deficient cells, which showed decreased levels of expression in caspase-3, activated caspase-9, Bax, p53, activated caspase-8, and Fas/CD95, as well as an increase in Bcl-2 expression.Although Dkk-3 expression was observed in most of human ovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer MCAS cells.
収録刊行物
-
- International Journal of Gynecological Cancer
-
International Journal of Gynecological Cancer 25 (3), 372-379, 2015-03
BMJ
- Tweet
キーワード
- Death Domain Receptor Signaling Adaptor Proteins
- Cell Survival
- Apoptosis
- DNA Fragmentation
- Cell Line, Tumor
- Humans
- fas Receptor
- RNA, Small Interfering
- Wnt Signaling Pathway
- Adaptor Proteins, Signal Transducing
- Cell Proliferation
- bcl-2-Associated X Protein
- Ovarian Neoplasms
- Caspase 8
- Caspase 1
- DNA, Neoplasm
- Adenocarcinoma, Mucinous
- Caspase 9
- Mitochondria
- Proto-Oncogene Proteins c-bcl-2
- Intercellular Signaling Peptides and Proteins
- Female
- Chemokines
- Tumor Suppressor Protein p53