| セッション情報 |
The 2nd JSGE International Topic Conference Poster Session
Cytokine
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| タイトル |
IT-P-18：The Regulation of Lymphotoxin-β is Involved in the Higher-order Chromatin Conformation of the TNF/LT Locus in Hepatocellular Carcinoma Cells
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| 演者 |
Watanabe Takehisa（Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Japan） |
| 共同演者 |
Tateyama Masakuni（Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Japan）, Tanaka Motohiko（Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Japan）, Ojima Hidenori（Division of Molecular Pathology, National Cancer Center Research Institute, Japan.）, Kanai Yae（Division of Molecular Pathology, National Cancer Center Research Institute, Japan.）, Ishihara Ko（Priority Organization for Innovation and Excellence, Kumamoto University, Japan）, Nakao Mitsuyosi（Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Japan）, Sasaki Yutaka（Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Japan） |
| 抄録 |
The tumor necrosis factor（TNF）superfamily members, TNF（initially termed TNF-α）, lymphotoxin-α（LTα）, and lymphotoxin-β（LTβ）, are major pro-inflammatory cytokines that mediate inflammatory responses. In addition to their physiological roles, the aberrant or unbalanced expression of these cytokines is linked to pathological conditions, including cancer development. Especially, LTβ expression is significantly involved in liver inflammation, regeneration and hepatocellular carcinomas（HCCs）. The TNF/LT genes are sequentially located and differently regulated. However, the regulatory mechanisms have been poorly understood. We have demonstrated a transcriptional mechanism and higher-order chromatin regulation in the TNF/LT locus with chromosome conformation capture（3C）analyses. In this context, we identified at least four CTCF/cohesin-enriched insulators and a TNF responsive TE2 enhancer in human hepatic cells. The interactions between TE2 enhancer and LTβ promoter, which activate LTβ gene transcription, were found to be regulated by insulator-mediated chromatin conformation. In addition, the results of the following immune-histochemical analyses of human HCC tissues to examine LTβ expression in vivo may support our finding. In conclusion, to investigate the relationship between LTβ expression and chromosomal conformation of the TNF/LT locus may provide a novel therapeutic strategy for chronic hepatitis as well as HCC. |
| 索引用語 |
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