論文 - 詳細
RRC ID | 45416 |
---|---|
著者 | Takata A, Terauchi M, Hiramitsu S, Uno M, Wakana K, Kubota T. |
タイトル | Dkk-3 induces apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer cells. |
ジャーナル | Int J Gynecol Cancer |
Abstract |
OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSIONS: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. |
巻・号 | 25(3) |
ページ | 372-9 |
公開日 | 2015-3-1 |
DOI | 10.1097/IGC.0000000000000340 |
PMID | 25514350 |
MeSH | Adaptor Proteins, Signal Transducing Adenocarcinoma, Mucinous / metabolism* Apoptosis Caspase 1 / metabolism Caspase 8 / metabolism Caspase 9 / metabolism Cell Line, Tumor Cell Proliferation Cell Survival Chemokines DNA Fragmentation DNA, Neoplasm / metabolism* Death Domain Receptor Signaling Adaptor Proteins / metabolism* Female Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Mitochondria / metabolism* Ovarian Neoplasms / metabolism* Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Small Interfering Tumor Suppressor Protein p53 / metabolism Wnt Signaling Pathway bcl-2-Associated X Protein / metabolism fas Receptor / metabolism |
IF | 2.095 |
引用数 | 15 |
WOS 分野 | OBSTETRICS & GYNECOLOGY ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 | OMC-3(RCB0755) JHOC-5(RCB1520) |