TY - JOUR
T1 - Circulating IGF-1 promotes prostate adenocarcinoma via FOXO3A/BIM signaling in a double-transgenic mouse model
AU - Wang, Shuang
AU - Wang, Ning
AU - Yu, Bin
AU - Cao, Mingxing
AU - Wang, Yanlong
AU - Guo, Yuqi
AU - Zhang, Yanli
AU - Zhang, Ping
AU - Yu, Xiao
AU - Wang, Shujing
AU - Zeng, Li
AU - Liang, Bin
AU - Li, Xin
AU - Wu, Yingjie
N1 - Funding Information:
Acknowledgements This study was supported by the Nature Science Foundation of China (NSFC) No. 81471000, No. 31871163, and Ministry of Science and Technology (No. 2014DFA32120) to Yingjie Wu.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/9/5
Y1 - 2019/9/5
N2 - 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.
AB - 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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U2 - 10.1038/s41388-019-0880-9
DO - 10.1038/s41388-019-0880-9
M3 - Article
C2 - 31312023
AN - SCOPUS:85069045890
SN - 0950-9232
VL - 38
SP - 6338
EP - 6353
JO - Oncogene
JF - Oncogene
IS - 36
ER -