Transcriptome analysis reveals that Müllerian inhibiting substance regulates signaling pathways that contribute to endometrial carcinogenesis

Chung,Youn Jee; Kim,Hyun Jung; Park,Sang Ho; Yoon,Joo Hee; Kim,Mee Ran; Nam,Suk Woo; MacLaughlin,David T.; Donahoe,Patricia K.; Kim,Jang Heub

doi:10.3892/ijo.2015.2920

May-2015 Volume 46 Issue 5

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May-2015 Volume 46 Issue 5

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Article

Transcriptome analysis reveals that Müllerian inhibiting substance regulates signaling pathways that contribute to endometrial carcinogenesis

Authors:
- Youn Jee Chung
- Hyun Jung Kim
- Sang Ho Park
- Joo Hee Yoon
- Mee Ran Kim
- Suk Woo Nam
- David T. MacLaughlin
- Patricia K. Donahoe
- Jang Heub Kim
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Pages: 2039-2046
|
Published online on: March 6, 2015

https://doi.org/10.3892/ijo.2015.2920
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Abstract

Müllerian inhibiting substance (MIS) has been shown to inhibit growth of a number of tumors in vitro and/or in vivo, but the downstream pathways which it regulates are not fully understood. In the present study we show that MIS type II receptor was highly expressed in AN3CA cells, a cell line derived from human endometrial cancer cell in which MIS-treatment caused a reduction of cell viability, and induced cellular apoptosis and genes involved cell cycle arrest. To understand the genome-wide effects of MIS on gene regulation, we performed serial gene expression analyses from 0 to 96 h at 24 h intervals after treating AN3CA cells with MIS. Transcriptomic analysis of molecular changes induced by MIS identified 2,688 differentially expressed genes that were significantly up- or down-regulated during the 96 h study period. When the 2,688 differentially expressed genes were mapped to known biological processes, Wnt-, cancer-, proteolysis-, cytoskeleton-, cell cycle-, apoptosis-, and MAPK-signaling pathways emerged as the functions most significantly changed by MIS in AN3CA cells. Furthermore, western blot analysis validated that protein expression of cell cycle inhibitory genes, apoptotic protease activating factor-1 (APAF-1), β-catenin-interacting protein (ICAT), Rb related protein 130 (p130), and inhibitor of disheveled Dvl and Axin complex (IDAX), were gradually increased over the time of the study, whereas downstream cell cycle activating genes, cyclin-dependent kinase 2 (CDK2) and phospho-c-Jun were downregulated in MIS-treated AN3CA cells. These transcriptome analyses support previous observations that MIS functions as a tumor suppressor, potentially by regulating signaling pathways that could contribute to endometrial carcinogenesis, and indicating that MIS should be considered as a potential treatment for endometrial cancer.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Transcriptome analysis reveals that Müllerian inhibiting substance regulates signaling pathways that contribute to endometrial carcinogenesis

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Abstract

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