Elucidation of EVI1 molecular network in pancreatic carcinogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860263
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: The University of Tokyo
• Principal Investigator: TANAKA Mariko 東京大学, 医学(系)研究科(研究院), 助教 (50645710)
• Research Collaborator: 深山 正久 ; 石川 俊平 ; 砂河 孝行 ; 鈴木 洋
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 膵癌 / 発癌 / 分化異常 / EVI1 / KRAS / microRNA

Outline of Final Research Achievements

Pancreatic cancer typically manifests a very poor prognosis. The precise mechanism of pancreatic carcinogensis is still unclear. Although an activating point mutation of KRAS is an early event in pancreatic carcinogenesis, it remains unclear whether KRAS mutation is solely responsible for initiation of pancreatic carcinogenesis. By tracking potential transcriptional regulators of gastric epithelial genes in pancreatic neoplasms, we found that overt expression of ecotropic viral integration site 1 (EVI1) oncoprotein is a hallmark of human pancreatic cancer and its precursors. In pancreatic cancer cells, EVI1 poses the oncogenic role by upregulating KRAS expression through suppression of a potent KRAS suppressor, miR-96. Results suggest that EVI1 oncoprotein and KRAS mutation converge on activation of the KRAS pathway in the early phase of pancreatic carcinogenesis and implicate EVI1 and/or miR-96 as candidate early markers and therapeutic targets in pancreatic cancer.

Free Research Field

病理学