self-renewing pten--tp53-- protospheres produce metastatic adenocarcinoma cell lines with multipotent progenitor activity自我更新的ptenu2014u2014tp53 protospheres生产转移性腺癌与多能祖细胞系的活动.pdfVIP

Self-Renewing Pten-/-TP53-/- Protospheres Produce Metastatic Adenocarcinoma Cell Lines with Multipotent Progenitor Activity 1,2 1 1¤ 1 1 1 Wassim Abou-Kheir , Paul G. Hynes , Philip Martin , Juan Juan Yin , Yen-Nien Liu , Victoria Seng , 1 1 1 Ross Lake , Joshua Spurrier , Kathleen Kelly * 1 Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Abstract Prostate cancers of luminal adenocarcinoma histology display a range of clinical behaviors. Although most prostate cancers are slow-growing and indolent, a proportion is aggressive, developing metastasis and resistance to androgen deprivation treatment. One hypothesis is that a portion of aggressive cancers initiate from stem-like, androgen-independent tumor- propagating cells. Here we demonstrate the in vitro creation of a mouse cell line, selected for growth as self-renewing stem/ progenitor cells, which manifests many in vivo properties of aggressive prostate cancer. Normal mouse prostate epithelium containing floxed Pten and TP53 alleles was subjected to CRE-mediated deletion in vitro followed by serial propagation as protospheres. A polyclonal cell line was established from dissociated protospheres and subsequently a clonal daughter line was derived. Both lines demonstrate a mature luminal phenotype in vitro. The established lines contain a stable minor population of progenitor cells with protosphere-form