ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(20):6289-6300. doi:10.7150/jca.60700 This issue Cite
Research Paper
Functional profiles of Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) in primarily cultured endometrial cancer cells
1. Department of Obstetrics and Gynecology, St. Vincent's hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
2. Department of Obstetrics and Gynecology, Seoul St. Mary's hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Abstract
Background: Müllerian inhibiting substance/anti-Müllerian 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 β-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 functions as a tumor suppressor and may be an effective therapeutic agent in endometrial cancer.
Keywords: anti-Müllerian hormone, Müllerian inhibiting substance, endometrial cancer, Wnt signaling pathway
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