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  • 1
    Publication Date: 2008-10-24
    Description: The existence of prostate stem cells (PSCs) was first postulated from the observation that normal prostate regeneration can occur after repeated cycles of androgen deprivation and replacement in rodents. Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis, it is important to define specific markers for normal PSCs. Several cell-surface markers have been reported to identify candidate PSCs, including stem cell antigen-1 (Sca-1, also known as Ly6a), CD133 (Prom1) and CD44 (refs 3-10). However, many non-PSCs in the mouse prostate also express these markers and thus identification of a more defined PSC population remains elusive. Here we identify CD117 (c-kit, stem cell factor receptor) as a new marker of a rare adult mouse PSC population, and demonstrate that a single stem cell defined by the phenotype Lin(-)Sca-1(+)CD133(+)CD44(+)CD117(+) can generate a prostate after transplantation in vivo. CD117 expression is predominantly localized to the region of the mouse prostate proximal to the urethra and is upregulated after castration-induced prostate involution-two characteristics consistent with that of a PSC marker. CD117(+) PSCs can generate functional, secretion-producing prostates when transplanted in vivo. Moreover, CD117(+) PSCs have long-term self-renewal capacity, as evidenced by serial isolation and transplantation in vivo. Our data establish that single cells in the adult mouse prostate with multipotent, self-renewal capacity are defined by a Lin(-)Sca-1(+)CD133(+)CD44(+)CD117(+) phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leong, Kevin G -- Wang, Bu-Er -- Johnson, Leisa -- Gao, Wei-Qiang -- England -- Nature. 2008 Dec 11;456(7223):804-8. doi: 10.1038/nature07427. Epub 2008 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18946470" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/metabolism/*physiology/*transplantation ; Animals ; Antigens, Surface/genetics ; Epithelium/metabolism ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; Prostate/*cytology/*growth & development/metabolism/secretion ; Proto-Oncogene Proteins c-kit/genetics ; *Stem Cell Transplantation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-05-17
    Description: The proto-oncogenes ETV1, ETV4 and ETV5 encode transcription factors in the E26 transformation-specific (ETS) family, which includes the most frequently rearranged and overexpressed genes in prostate cancer. Despite being critical regulators of development, little is known about their post-translational regulation. Here we identify the ubiquitin ligase COP1 (also known as RFWD2) as a tumour suppressor that negatively regulates ETV1, ETV4 and ETV5. ETV1, which is mutated in prostate cancer more often, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs and was 50-fold more stable than wild-type ETV1. Almost all patient translocations render ETV1 insensitive to COP1, implying that this confers a selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. Combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein, and elevated ETV1 protein while lacking a translocation event. These findings identify COP1 as a tumour suppressor whose downregulation promotes prostatic epithelial cell proliferation and tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vitari, Alberto C -- Leong, Kevin G -- Newton, Kim -- Yee, Cindy -- O'Rourke, Karen -- Liu, Jinfeng -- Phu, Lilian -- Vij, Rajesh -- Ferrando, Ronald -- Couto, Suzana S -- Mohan, Sankar -- Pandita, Ajay -- Hongo, Jo-Anne -- Arnott, David -- Wertz, Ingrid E -- Gao, Wei-Qiang -- French, Dorothy M -- Dixit, Vishva M -- England -- Nature. 2011 May 15;474(7351):403-6. doi: 10.1038/nature10005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21572435" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Carrier Proteins/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; DNA-Binding Proteins/genetics/metabolism ; Humans ; Male ; Mice ; Nuclear Proteins/deficiency/*metabolism ; PTEN Phosphohydrolase/deficiency ; Prostatic Neoplasms/metabolism/pathology ; Protein Binding ; Proto-Oncogene Proteins c-ets/*metabolism ; Transcription Factors/genetics/metabolism ; Tumor Suppressor Proteins/*metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-08-13
    Description: Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Xiao-yang -- Li, Wei -- Lv, Zhuo -- Liu, Lei -- Tong, Man -- Hai, Tang -- Hao, Jie -- Guo, Chang-long -- Ma, Qing-wen -- Wang, Liu -- Zeng, Fanyi -- Zhou, Qi -- England -- Nature. 2009 Sep 3;461(7260):86-90. doi: 10.1038/nature08267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19672241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology/physiology ; Cell Dedifferentiation/physiology ; Cell Line ; Cell Lineage ; Cellular Reprogramming ; Embryo, Mammalian/cytology/embryology/metabolism ; Embryonic Stem Cells/cytology/physiology ; Female ; Fibroblasts/cytology ; Gene Expression Profiling ; Genetic Complementation Test ; Male ; Mice ; Mice, SCID ; Pluripotent Stem Cells/cytology/*physiology ; *Polyploidy ; Pregnancy ; *Reproductive Techniques ; Survival Rate ; Teratoma
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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