Functional profiles of Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) in primarily cultured endometrial cancer cells

作者：Sang Il Kim, Joo Hee Yoon, Soo Young Hur · 发表于：Journal of Cancer · 年份：2021 · DOI：10.7150/jca.60700 · 被引用次数：8 · 研究领域：Genetic Syndromes and Imprinting、Kruppel-like factors research、Reproductive Biology and Fertility

Background: Mllerian inhibiting substance/anti-Mllerian hormone (MIS/AMH) inhibits proliferation of MIS/AMH receptor-expressing gynecologic tumors in vivo and in vitro, but the underlying mechanisms have not been fully defined. This study aimed to investigate the expression of MIS/AMH type II receptor (MIS/AMHRII) in endometrial cancer, to identify the mechanism of growth inhibition in MIS/AMH-treated endometrial cancer cells, and to evaluate the clinical significance of MIS/AMH as an effective targeted therapy for MIS/AMH receptor-expressing tumors. Methods: We used tissue samples from 10 patients with total hysterectomy for endometrial cancer. To identify involved signaling pathways, we performed western blotting on apoptosis-, cell cycle-, Wnt signaling-, and autophagy-related proteins. Results: MIS/AMHRII was highly expressed on the cell membrane of endometrial cancer tissues and primarily cultured endometrial cancer cells. We also found that MIS/AMH treatment reduced cell viability, induced cell cycle arrest, and increased apoptosis. MIS/AMH treatment induced upregulation of -catenin-interacting protein (ICAT) and inhibition of the Dvl and Axin complex (IDAX) but downregulation of phospho-c-Jun in the Wnt signaling pathway. Conclusions: MIS/AMH inhibits the growth of MIS/AMH receptor-expressing endometrial cancer cells through regulation of autophagy, apoptosis, and cell cycle pathways, as well as inhibition of Wnt signaling pathways. These data suggest that MIS/AMH func...