Aiko Takata1, Masakazu Terauchi, Shiro Hiramitsu, Masaya Uno, Kimio Wakana, Toshiro Kubota. 1. Departments of *Comprehensive Reproductive Medicine, and †Women's Health, Tokyo Medical and Dental University; and ‡Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
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.
OBJECTIVE:Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in humancancers. 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 humanovarian 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 humanovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in humanmucinous ovarian cancer MCAS cells.
Authors: Francesca Ricci; Federica Guffanti; Roberta Affatato; Laura Brunelli; Pastorelli Roberta; Robert Fruscio; Patrizia Perego; Maria Rosa Bani; Giovanna Chiorino; Andrea Rinaldi; Francesco Bertoni; Maddalena Fratelli; Giovanna Damia Journal: Am J Cancer Res Date: 2020-02-01 Impact factor: 6.166
Authors: Hemn Mohammadpour; Ali Akbar Pourfathollah; Mahin Nikougoftar Zarif; Amir Ali Shahbazfar Journal: Sci Rep Date: 2016-06-22 Impact factor: 4.379