J Cancer 2021; 12(20):6289-6300. doi:10.7150/jca.60700 This issue

Research Paper

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

Sang Il Kim1, Joo Hee Yoon1, Soo Young Hur2✉

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

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Kim SI, Yoon JH, Hur SY. Functional profiles of Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) in primarily cultured endometrial cancer cells. J Cancer 2021; 12(20):6289-6300. doi:10.7150/jca.60700. Available from https://www.jcancer.org/v12p6289.htm

File import instruction

Abstract

Graphic 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