Elucidation of development of pancreatic neuroendocrine tumors mediated by abnormal amino acid metabolism using a mouse model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nagoya University
• Principal Investigator: Hori Mika 名古屋大学, 環境医学研究所, 講師 (60598043)
• Co-Investigator(Kenkyū-buntansha): 筆宝 義隆 千葉県がんセンター(研究所), 発がん制御研究部, 研究所長 (30359632)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵神経内分泌腫瘍 / グルカゴン / 肝転移 / 遺伝子改変マウス

Outline of Final Research Achievements

In glucagon gene-deficient mice in which the glucagon gene coding region was replaced with green fluorescent protein GFP cDNA, pancreatic neuroendocrine tumors (panNET) developed from the age of 10 months, and numerous GFP-positive cells were observed in the liver. Liver metastases were observed in some male mice that survived to 15 months of age. Endocrine granule markers Chromogranin A and Synaptophysin were weakly positive in liver metastases. GFP-positive cells observed in the liver showed characteristics of pancreatic endocrine or immune cells. Through genome analysis of panNET, we identified 43 genes related to cell proliferation and invasion.

Free Research Field

病態医科学

Academic Significance and Societal Importance of the Research Achievements

ヒトにおいてもグルカゴン受容体遺伝子のホモ型変異により多発性のpanNETが発生し、非常に稀なMahvash disease と呼ばれている。グルカゴン遺伝子欠損マウスでは、肝臓で観察された GFP陽性細胞から微小転移、肝転移巣と転移が進展することが予想され、本マウスはMahvash disease及び肝転移機構の解析に良いモデルとなりうる。