期刊
ONCOGENE
卷 20, 期 18, 页码 2264-2272出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204312
关键词
mammary; stem cell; cancer risk; cellular senescence; MMTV
The reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. In a study of FVB/ N mice with the transgene, WAP-TGF beta1, we discovered that mammary epithelial stem tells were prematurely aged due to ectopic expression of TGF-beta1. To test whether premature aging of mammary epithelial stem cells would have an impart on susceptibility or resistance to mammary cancer, female littermates from FVB/ N x WAP-TGF-beta1 mating were injected with mouse mammary tumor virus (MMTV) at 8-10 weeks of age. A total of 44 females were inoculated, maintained as breeders and observed for tumor development for up to 18 months. Only one mammary tumor appeared in 17 TGF-beta1 females while 15 were collected from 29 wild type sisters. Premalignant mammary epithelial cells in infected glands were identified by transplantation of single cell(1 x 10(5)) suspensions into nulliparous hosts and testing for hyperplastic outgrowth. Although the number of positive takes was significantly reduced with TGF-beta1 cells, both MMTV-infected TGF-beta1 and wild type cells produced hyperplastic outgrowths suggesting that premalignant transformation was achieved in each group. The results suggest a positive correlation between the procreative life-span of mammary epithelial stem cells and mammary cancer risk.
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