Involvement of the melanocortin receptor pathway in pancreatic and colorectal carcinogenesis and its application to cancer prevention

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290049
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

腫瘍学　がん化学予防