Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression
Abstract Aims/Introduction Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti‐prostate cancer effect of glucagon‐like peptide‐1 receptor (GLP‐1R) agonist exendin‐4. The attenuation of cell proliferation in the prostate cancer cell line was depend...
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doaj-46b73efe4bc4460ab61d39d90ff1417d2021-05-02T15:14:09ZengWileyJournal of Diabetes Investigation2040-11162040-11242020-09-011151137114910.1111/jdi.13247Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progressionToru Shigeoka0Takashi Nomiyama1Takako Kawanami2Yuriko Hamaguchi3Tsuyoshi Horikawa4Tomoko Tanaka5Shinichiro Irie6Ryoko Motonaga7Nobuya Hamanoue8Makito Tanabe9Kazuki Nabeshima10Masatoshi Tanaka11Toshihiko Yanase12Daiji Kawanami13Department of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Urology School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanDepartment of Pathology School of Medicine Fukuoka University Fukuoka JapanDepartment of Urology School of Medicine Fukuoka University Fukuoka JapanResearch institute for Islet Biology Fukuoka University Fukuoka JapanDepartment of Endocrinology and Diabetes Mellitus School of Medicine Fukuoka University Fukuoka JapanAbstract Aims/Introduction Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti‐prostate cancer effect of glucagon‐like peptide‐1 receptor (GLP‐1R) agonist exendin‐4. The attenuation of cell proliferation in the prostate cancer cell line was dependent on GLP‐1R expression. 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. Materials and 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 polymerase chain reaction. Cell proliferation was examined by growth curves and bromodeoxyuridine incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were carried out 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 carried out by implanting ALVA‐41‐GLP‐1R cells showed 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 might be a potential therapy for prostate cancer.https://doi.org/10.1111/jdi.13247Cell cycleGlucagon‐like peptide‐1 receptorProstate cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression Journal of Diabetes Investigation Cell cycle Glucagon‐like peptide‐1 receptor Prostate cancer |
author_facet |
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 |
author_sort |
Toru Shigeoka |
title |
Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
title_short |
Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
title_full |
Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
title_fullStr |
Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
title_full_unstemmed |
Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
title_sort |
activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression |
publisher |
Wiley |
series |
Journal of Diabetes Investigation |
issn |
2040-1116 2040-1124 |
publishDate |
2020-09-01 |
description |
Abstract Aims/Introduction Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti‐prostate cancer effect of glucagon‐like peptide‐1 receptor (GLP‐1R) agonist exendin‐4. The attenuation of cell proliferation in the prostate cancer cell line was dependent on GLP‐1R expression. 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. Materials and 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 polymerase chain reaction. Cell proliferation was examined by growth curves and bromodeoxyuridine incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were carried out 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 carried out by implanting ALVA‐41‐GLP‐1R cells showed 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 might be a potential therapy for prostate cancer. |
topic |
Cell cycle Glucagon‐like peptide‐1 receptor Prostate cancer |
url |
https://doi.org/10.1111/jdi.13247 |
work_keys_str_mv |
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