Involvement of the melanocortin receptor pathway in pancreatic and colorectal carcinogenesis and its application to cancer prevention
| Project/Area Number |
25290049
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Takahashi Mami 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (90214973)
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| Co-Investigator(Kenkyū-buntansha) |
MUTOH Michihiro 国立研究開発法人 国立がん研究センター, 社会と健康研究センター 予防研究部 予防研究室, 室長 (30392335)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | メラノコルチン受容体 / 膵臓がん / 大腸がん / がん予防 / アグーチ |
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| Outline of Final Research Achievements |
The Ay allele promoted pancreatic carcinogenesis in Ptf1a-KrasG12D mice and azoxymethane (AOM)-induced colorectal carcinogenesis in diabetic KK mice. Increased expression of CSF1 and accumulation of macrophages was observed in pancreatic carcinoma tissues in Ptf1a-KrasG12D-Ay mice and AOM-induced colorectal carcinoma tissues in KK-Ay mice. The agouti overexpression in pancreatic cancer cell lines established from Ptf1a-KrasG12D mice increases the expression of adipogenesis-related gene X via antagonizing MCRs. The gene X product significantly elevated CSF1 expression. Expression of the gene X was decreased by treatment with forskolin, which elevates intracellular cAMP and stimulates downstream pathways of MCRs. However, effects of forskolin on inflammatory factors were different among cell lines and the effects on carcinogenesis was supposed to be not consistent.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] A^y allele promotes azoxymethane-induced colorectal carcinogenesis via macrophage migration in hyperlipidemic/diabetic KK mice.2013
Author(s)
Ito, K., Ishigamori, R., Mutoh, M., Ohta, T., Imai, T., Takahashi, M
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Journal Title
Cancer Sci.
Volume: (in press)
Issue: 7
Pages: 835-843
DOI
Related Report
Peer Reviewed
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[Presentation] Increase of pancreatic cancer development in pancreas-specific K-ras mutant mice by crossing with obesity Ay mice and involvement of the M-CSF.2016
Author(s)
Takahashi, M.,Ishigamori, R.,Mutoh, M., Fujii, G., Miyamoto, S., Imai, T.
Organizer
Tenth AACR-JCA Joint Conference
Place of Presentation
米国ハワイ州
Year and Date
2016-02-19
Related Report
Int'l Joint Research
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