Trophoblastic neoplasms express fatty acid synthase, which may be a therapeutic target via its inhibitor C93

Stefanie M. Ueda, Tsui Lien Mao, Francis P. Kuhajda, Chanont Vasoontara, Robert L. Giuntoli, Robert E. Bristow, Robert J. Kurman, Ie Ming Shih*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Fatty acid synthase (FASN) is an emerging tumor-associated marker and a promising antitumor therapeutic target. In this study, we analyzed the expression of FASN in normal and molar placentas, as well as gestational trophoblastic neoplasia, and assessed the effects of a new FASN inhibitor, C93, on cellular proliferation and apoptosis in choriocarcinoma cells. Using a FASN-specific monoclonal antibody, we found that FASN immunoreactivity was detected in the cytotrophoblast and intermediate (extravillous) trophoblast of normal and molar placentas, as well as in placental site nodules. All choriocarcinomas (n = 33), 90% of epithelioid trophoblastic tumors (n = 20), and 60% of placental site trophoblastic tumors (n = 10) exhibited FASN positivity. FASN expression was further confirmed in vitro by Western blot and real-time PCR. Treatment of JEG3 and JAR cells with C93 induced significant apoptosis through the caspase-3/caspase-9/poly(ADP)ribose polymerase pathway. Cell cycle progression was not affected by the inhibitor. In summary, the data indicate that FASN is expressed in the majority of gestational trophoblastic neoplasias, and is essential for choriocarcinoma cells to survive and escape from apoptosis. FASN inhibitors such as C93 warrant further investigation as targeted therapeutic agents for metastatic and chemoresistant gestational trophoblastic neoplasia.

原文英語
頁(從 - 到)2618-2624
頁數7
期刊American Journal of Pathology
175
發行號6
DOIs
出版狀態已出版 - 2009
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