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

Shuang Wang, Ning Wang, Bin Yu, Mingxing Cao, Yanlong Wang, Yuqi Guo, Yanli Zhang, Ping Zhang, Xiao Yu, Shujing Wang, Li Zeng, Bin Liang, Xin Li, Yingjie Wu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)6338-6353
Number of pages16
JournalOncogene
Volume38
Issue number36
DOIs
StatePublished - Sep 5 2019

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wang, S., Wang, N., Yu, B., Cao, M., Wang, Y., Guo, Y., Zhang, Y., Zhang, P., Yu, X., Wang, S., Zeng, L., Liang, B., Li, X., & Wu, Y. (2019). Circulating IGF-1 promotes prostate adenocarcinoma via FOXO3A/BIM signaling in a double-transgenic mouse model. Oncogene, 38(36), 6338-6353. https://doi.org/10.1038/s41388-019-0880-9