Identification of resistance genes in the process of tumor progression

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860303
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: OKUMURA Kazuhiro 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, 客員研究員 (80584680)
• 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)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: DMBA-TPA多段階皮膚発がん / 皮膚腫瘍抵抗性遺伝子座 / 日本産野生由来近交系 / コンジェニックマウス / BACトランスジェニックマウス

Outline of Final Research Achievements

Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to early-stage and late-stage chemically induced skin papillomas on chromosome 7 and 4 by analyzing a large number of [(FVB/N×MSM/Ms)×FVB/N] F1 backcross mice. In this report, we describe a sub-congenic mapping analysis of the loci on chromosome 7 and 4. We used linkage analysis and congenic mouse strains to refine the location of Stmm (Skin tumor modifier of MSM) 1 and 3 loci within a genetic interval of about 2-5 cM, respectively. The parathyroid hormone (Pth) gene was found in the vicinity of Stmm1b. Here, we report a genetic polymorphism located in the Pth gene, which produces Val/Met pro-Pth variants. Skin carcinogenesis experiments using MSM-BAC transgenic mouse lines FVB/N-Tg(MSMg01-047A16) showed MSM-Pth alleles conferred resistance to tumors. These results suggested that Pth might be a candidate responsible gene for Stmm1b.

Free Research Field

マウス遺伝学、がん分子生物学