Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice

被引:230
作者
DiGiovanni, J
Kiguchi, K
Frijhoff, A
Wilker, E
Bol, DK
Beltrán, L
Moats, S
Ramirez, A
Jorcano, J
Conti, C
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX 78957 USA
[2] Ciemat Inst, Dept Cell & Mol Biol, Madrid 28040, Spain
关键词
D O I
10.1073/pnas.97.7.3455
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium, Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice greater than or equal to 6 months of age (38 mice total) was 50%, The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
引用
收藏
页码:3455 / 3460
页数:6
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