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

• DOI: 10.3892/ijo.2015.2920
• Publication Date: 2015-03-06T10:26:24Z
• 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
• Keywords: 0301 basic medicine; Receptors, Peptide; Retinoblastoma-Like Protein p130; Proto-Oncogene Proteins c-jun; Gene Expression Profiling; Blotting, Western; Cyclin-Dependent Kinase 2; Intracellular Signaling Peptides and Proteins; Articles; Endometrial Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Apoptotic Protease-Activating Factor 1; Cell Line, Tumor; Humans; Female; Receptors, Transforming Growth Factor beta; Adaptor Proteins, Signal Transducing; Signal Transduction

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