title: The role of tumor suppressor menin in IL-6 regulation in mouse islet tumor cells.
abstract: Menin is a gene product of multiple endocrine neoplasia type1 (Men1), an inherited familial cancer syndrome characterized by tumors of endocrine tissues. To gain insight about how menin performs an endocrine cell-specific tumor suppressor function, we investigated the possibility that menin was integrated in a cancer-associated inflammatory pathway in a cell type-specific manner. Here, we showed that the expression of IL-6, a proinflammatory cytokine, was specifically elevated in mouse islet tumor cells upon depletion of menin and Men(-/-) MEF cells, but not in hepatocellular carcinoma cells. Histone H3 lysine (K) 9 methylation, but not H3 K27 or K4 methylation, was involved in menin-dependent IL-6 regulation. Menin occupied the IL-6 promoter and recruited SUV39H1 to induce H3 K9 methylation. Our findings provide a molecular insight that menin-dependent induction of H3 K9 methylation in the cancer-associated interleukin gene might be linked to preventing endocrine-specific tumorigenesis.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Tae-Yang
authors.initials: TY
authors.lastname: Song
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Lim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea; C&C Research Laboratories, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Byungho
authors.initials: B
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Biomedical Sciences and Biochemistry and Molecular Biology, National Creative Research Center for Epigenome Reprogramming Network, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: echo@skku.edu.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006637:Histamine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D007340:Insulinoma / Q000235:genetics* / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; C105373:MEN1 protein, human; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D006637:Histamine N-Methyltransferase
keywords: Histone; Histone methylation; Men1; Menin; Tumor suppressor