期刊
ONCOGENE
卷 29, 期 32, 页码 4543-4554出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.186
关键词
mammary tumors; stem cells; Notch1
资金
- Canadian Institute of Heath Research (CIHR)
- Canada Research Chair
Members of the Notch family are involved in the development of breast cancer in animal models and in humans. In young transgenic mice, expressing intracellular activated Notch1 (N1(IC)) in mammary cells, we found that CD24(+) CD29(high) progenitor cells had enhanced survival, and were expanded through a cyclin D1-dependent pathway. This expansion positively correlated with the later cyclin D1-dependent formation of basal-like ductal tumors. This expanded population exhibited abnormal differentiation skewed toward the basal cells, showed signs of pre-malignancy (low PTEN/p53 and high c-myc) and contained stem cells with impaired self-renewal in vivo, and more numerous multipotent, ductal-restricted progenitors. Our data suggest that N1(IC) can favor transformation of progenitor cells early in life through a cyclin D1-dependent pathway. Oncogene (2010) 29, 4543-4554; doi: 10.1038/onc.2010.186; published online 21 June 2010
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