Identification of cancer-related gene polymorphisms by genetic integration of mouse and human

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06817
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Okumura Kazuhiro 千葉県がんセンター(研究所), がんゲノムセンター 腫瘍ゲノム研究室, 研究員 (80584680)
• Co-Investigator(Kenkyū-buntansha): 磯貝 恵理子 千葉県がんセンター(研究所), 発がん研究グループ 実験動物研究室, 上席研究員 (40300917)
• Co-Investigator(Renkei-kenkyūsha): Wakabayashi Yuichi 千葉県がんセンター研究所, 実験動物研究室, 室長 (40303119) ; Taya Chouji 公益財団法人東京都医学総合研究所, 基盤技術研究センター・動物実験開発室, 室長 (90175456) ; Sakakibara Yasubumi 慶應義塾大学, 理工学部, 教授 (10287427) ; Matsuda Koichi 東京大学, 医科学研究所, 准教授 (90401257)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: DMBA-TPA多段階皮膚発がん / 日本産野生マウス系統 / 発がん抵抗性/感受性遺伝子 / 副甲状腺ホルモン

Outline of Final Research Achievements

Using a forward genetics approach to map loci in a mouse skin cancer model, we previously identified a genetic locus, Skin Tumor modifier of MSM 1 (Stmm1) on chromosome 7, conferring strong Tumor resistance. Here, we report that serum intact-PTH (iPTH) and a genetic polymorphism in Pth are important for skin Tumor resistance. We identified higher iPTH levels in sera from cancer-resistant MSM/Ms mice compared with susceptible FVB/NJ mice. Therefore, we performed skin carcinogenesis experiments with MSM-BAC transgenic mice (PthMSM-Tg) and Pth knockout heterozygous mice (Pth +/-). As a result, the higher amounts of iPTH in sera conferred stronger resistance to skin Tumors. Taken together, our data suggest that Pth is one of the genes responsible for Stmm1, and serum iPTH could serve as a prevention marker of skin cancer and a target for new therapies.

Free Research Field

がん遺伝学