2. Academic Validation
  3. Circulating IGF-1 promotes prostate adenocarcinoma via FOXO3A/BIM signaling in a double-transgenic mouse model

Circulating IGF-1 promotes prostate adenocarcinoma via FOXO3A/BIM signaling in a double-transgenic mouse model

  • Oncogene. 2019 Sep;38(36):6338-6353. doi: 10.1038/s41388-019-0880-9.
Shuang Wang 1 2 3,  Ning Wang 1 2 3,  Bin Yu 1 2,  Mingxing Cao 1 2 4,  Yanlong Wang 5,  Yuqi Guo 6,  Yanli Zhang 6,  Ping Zhang 7,  Xiao Yu 8,  Shujing Wang 9,  Li Zeng 1 2,  Bin Liang 10,  Xin Li 11 12 13,  Yingjie Wu 14 15 16 17 18
Affiliations

Affiliations

  • 1 Institute of Genome Engineered Animal Models for Human Diseases, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 2 National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 3 College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 4 College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, Heilongjiang, 157011, China.
  • 5 Department of Urology Surgery, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, Liaoning, 116033, China.
  • 6 Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA.
  • 7 Department of Endocrinology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116027, China.
  • 8 Department of Pathology, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 9 Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 10 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, CAS Center for Excellence in Animal Evolution and Genetics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China. liangb@mail.kiz.ac.cn.
  • 11 Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA. xl15@nyu.edu.
  • 12 Department of Urology, New York University Langone Medical Center, New York, NY, 10016, USA. xl15@nyu.edu.
  • 13 Perlmutter Cancer Institute, New York University Langone Medical Center, New York, NY, 10016, USA. xl15@nyu.edu.
  • 14 Institute of Genome Engineered Animal Models for Human Diseases, Dalian Medical University, Dalian, Liaoning, 116044, China. yingjiewu@dmu.edu.cn.
  • 15 National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, Liaoning, 116044, China. yingjiewu@dmu.edu.cn.
  • 16 College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China. yingjiewu@dmu.edu.cn.
  • 17 Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA. yingjiewu@dmu.edu.cn.
  • 18 Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn Mount Sinai School of Medicine, New York, NY, 10029, USA. yingjiewu@dmu.edu.cn.
PMID: 31312023 DOI: 10.1038/s41388-019-0880-9
Abstract

High circulating insulin-like growth factor-1 (IGF-1) levels increase the risk of prostate Cancer. However, whether circulating IGF-1 levels directly aggravate prostate Cancer remains elusive. In this study, we crossed a transgenic prostate adenocarcinoma mouse model, Hi-Myc mice, with a liver-specific IGF-1 transgenic mouse model (HIT) to increase their circulating IGF-1 levels to investigate the impact of the elevated circulating IGF-1 on prostate Cancer development in vivo. The Hi-Myc/HIT mice had increased incidence and invasiveness of prostate Cancer. IGF-1 elevation led to the accumulation of FOXO3A in the cytosol of prostate tumor cells and downregulation of its target gene Bim, which resulted in the Apoptosis inhibition and prostate Cancer overgrowth. The differential expressions of IGF-1R, FOXO3A, and Bim in the benign versus malignant prostate tissues supported a negative association between the FOXO3A/Bim axis and IGF-1R expression in human prostate adenocarcinoma. Our findings suggest that targeting the IGF-1/FOXO3A/Bim signaling axis could be an attractive strategy for prostate Cancer prevention or treatment.

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