Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway

Park,Sang Ho; Chung,Youn Jee; Song,Jae Yen; Kim,Sang Il; Pépin,David; MacLaughlin,David T.; Donahoe,Patricia K.; Kim,Jang Heub

doi:10.3892/ijo.2017.3874

Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway

Authors:
- Sang Ho Park
- Youn Jee Chung
- Jae Yen Song
- Sang Il Kim
- David Pépin
- David T. MacLaughlin
- Patricia K. Donahoe
- Jang Heub Kim
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Affiliations: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul 137-140, Republic of Korea, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Published online on: February 13, 2017 https://doi.org/10.3892/ijo.2017.3874
Pages: 1022-1028

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Abstract

Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) has been suggested as a biotherapeutic agent in gynecological cancers that highly express the MIS/AMH type II receptors (MISRII/AMHRII) but the anticancer mechanisms by which MIS/AMH acts are not fully understood. Our experiments show that MIS/AMH inhibits ovarian cancer by deregulating the Wnt signal pathway via the β-catenin interacting protein (ICAT). MIS/AMH inhibition of ICAT by small interfering RNAs (siRNA) decreased ICAT driven ovarian cancer cell viability as measured by the methylthiazoltetrazolium assay, reversed cell cycle arrest and annexin V expression and diminished migration by scratch wound assay. Changes in expression of regulatory proteins were shown by western blotting. We determined that MIS/AMH upregulated ICAT in ovarian cancer cell line which caused decreased cell viability, cell cycle arrest and apoptosis. This effect, however, was blocked when ICAT was downregulated by siRNA. The present study demonstrates a role for ICAT in MIS/AMH mediated inhibition of the Wnt signaling pathway in ovarian cancer.

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