日本消化器病学会 アーカイブシステム

セッション情報 The 2nd JSGE International Topic Conference

5）Inflammation and Carcinogenesis in the Biliary Tract and Pancreas
タイトル IT5-4：

Identification of Inflammatory Signal-stimulating microRNA in Pancreatic Duct Cell Carcinoma
演者 Hamada　Shin（Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan）
共同演者 Satoh　Kennichi（Division of Gastroenterology, Tohoku University Graduate School of Medicine, JapanDELIMITERDivision of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Japan）, Masamune　Atsushi（Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan）, Shimosegawa　Tooru（Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan）
抄録 Pancreatic duct cell carcinoma（PDAC）is a lethal disease due to the invasive growth and rapid dissemination. PDAC shows a characteristic histological feature, desmoplasia which results from continuous inflammation within cancer tissue. Numerous studies indicated that the desmoplasia itself could be a defender of cancer cells, yielding physical barrier and growth support. Therefore, clarifying the cancer cell function affected by the continuous inflammation could identify critical mechanism which regulates invasive growth of PDAC. We focused on the differentially expressed microRNAs in PDAC, since microRNA is known to be a potent, comprehensive regulator of cellular functions.
We carried out microarray analysis by comparing microRNA expression profiles in PDAC and intraductal papillary mucinous neoplasm（IPMN）. As a result, novel microRNAs which regulate cellular motility were identified such as miR-126 and miR-197. In addition, miR-365 was found to be highly expressed in PDAC compared with IPMN.
Forced expression of miR-365 induced gemcitabine resistance in human PDAC cell lines Panc-1 and AsPC-1. Assessment of the intracellular signaling pathway identified that miR-365 increased NF-kappa B activity, evidenced by the I-kappa B-alpha degradation and elevated expression of phosphorylated-NF-kappa B. Potential target of miR-365 included multiple genes which regulate NF-kappa B activity. The miR-365/NF-kappa B axis could be a feed-forward loop which exacerbates inflammatory signal within pancreatic cancer cells.
索引用語