GLP-1 receptor expression in cancer cells

2019 Fiscal Year Research-status Report

• Project/Area Number: 18K08532
• Research Institution: Fukuoka University
• Principal Investigator: 野見山 崇 福岡大学, 医学部, 准教授 (10532559)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: GLP-1 / Cancer / Cell cycle / SKP2

Outline of Annual Research Achievements

Aim:. Here, we examined the relationship between human prostate cancer severity and GLP-1R expression, as well as the effect of forced expression of GLP-1R using a lentiviral vector.Methods: Prostate cancer tissues were extracted by prostatectomy and biopsy. GLP-1R was overexpressed in ALVA-41 cells using a lentiviral vector (ALVA-41-GLP-1R cells). GLP-1R expression was detected by immunohistochemistry and quantitative PCR. Cell proliferation was examined by growth curves and BrdU incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were performed using a xenografted model. Results:GLP-1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP-1R expression and functions were confirmed in ALVA-41-GLP-1R cells. Exendin-4 significantly decreased ALVA-41-GLP-1R cell proliferation in a dose-dependent manner. DNA synthesis and G1-to-S phase transition were inhibited in ALVA-41-GLP-1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA-41-GLP-1R cells treated with exendin-4. In vivo experiments performed by implanting ALVA-41-GLP-1R cells demonstrated that exendin-4 decreased prostate cancer growth by activation of GLP-1R overexpressed in ALVA41-GLP-1R cells. Conclusions: Forced expression of GLP-1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo. Therefore, GLP-1R activation may be a potential therapy for prostate cancer.

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

論文投稿済み。Journal of Diabetes Investigationにアクセプトされた。

Strategy for Future Research Activity

本研究を広く世間に通達する活動を行うとともに、今後の新たな研究発展に繋がるヒント模索する。

Research Products

• [Journal Article] Activation of overexpressed GLP-1R attenuates prostate cancer growth by inhibiting cell cycle progression (2020)
  • Author(s): Toru Shigeoka, Takashi Nomiyama, Takako Kawanami, Yuriko Hamaguchi, Tsuyoshi Horikawa, Tomoko Tanaka, Shinichiro Irie, Ryoko Motonaga, Nobuya Hamanoue, Makito Tanabe, Kazuki Nabeshima, Masatoshi Tanaka, Toshihiko Yanase, Daiji Kawanami
  • Journal Title: Journal of Diabetes Investigation Volume: NA Pages: NA
  • DOI: 10.1111/jdi.13247.
  • Peer Reviewed / Open Access