Identification of resistance genes in the process of tumor progression
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
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
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 / 日本野生由来近交系マウス / DMBA/TPA / 皮膚発がん抵抗性遺伝子座 / 副甲状腺ホルモン / 多段階皮膚発がん / 日本産野生マウス |
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.
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Report
(3 results)
Research Products
(12 results)