| Literature DB >> 31312023 |
Shuang Wang1,2,3, Ning Wang1,2,3, Bin Yu1,2, Mingxing Cao1,2,4, Yanlong Wang5, Yuqi Guo6, Yanli Zhang6, Ping Zhang7, Xiao Yu8, Shujing Wang9, Li Zeng1,2, Bin Liang10, Xin Li11,12,13, Yingjie Wu14,15,16,17,18.
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.Entities:
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Year: 2019 PMID： 31312023 DOI： 10.1038/s41388-019-0880-9
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867