IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v461y2009i7263d10.1038_nature08361.html
   My bibliography  Save this article

A luminal epithelial stem cell that is a cell of origin for prostate cancer

Author

Listed:
  • Xi Wang

    (Department of Medicine,
    Department of Genetics and Development,
    Center for Advanced Biotechnology and Medicine,
    and)

  • Marianna Kruithof-de Julio

    (Department of Medicine,
    Department of Genetics and Development,)

  • Kyriakos D. Economides

    (Center for Advanced Biotechnology and Medicine,
    UMDNJ–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).)

  • David Walker

    (Center for Advanced Biotechnology and Medicine,
    and
    Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).)

  • Hailong Yu

    (Center for Advanced Biotechnology and Medicine,
    and
    Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).)

  • M. Vivienne Halili

    (Center for Advanced Biotechnology and Medicine,
    and
    Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).)

  • Ya-Ping Hu

    (Center for Advanced Biotechnology and Medicine,
    and
    Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).)

  • Sandy M. Price

    (Center for Advanced Biotechnology and Medicine,
    and)

  • Cory Abate-Shen

    (and
    Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Center for Advanced Biotechnology and Medicine,
    UMDNJ–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA)

  • Michael M. Shen

    (Department of Medicine,
    Department of Genetics and Development,
    Center for Advanced Biotechnology and Medicine,
    and)

Abstract

In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.

Suggested Citation

  • Xi Wang & Marianna Kruithof-de Julio & Kyriakos D. Economides & David Walker & Hailong Yu & M. Vivienne Halili & Ya-Ping Hu & Sandy M. Price & Cory Abate-Shen & Michael M. Shen, 2009. "A luminal epithelial stem cell that is a cell of origin for prostate cancer," Nature, Nature, vol. 461(7263), pages 495-500, September.
    • Handle: RePEc:nat:nature:v:461:y:2009:i:7263:d:10.1038_nature08361
    DOI: 10.1038/nature08361
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature08361
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature08361?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tianyu Zhu & Huige Tong & Zhaozhen Du & Stephan Beck & Andrew E. Teschendorff, 2024. "An improved epigenetic counter to track mitotic age in normal and precancerous tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Hubert Pakula & Mohamed Omar & Ryan Carelli & Filippo Pederzoli & Giuseppe Nicolò Fanelli & Tania Pannellini & Fabio Socciarelli & Lucie Van Emmenis & Silvia Rodrigues & Caroline Fidalgo-Ribeiro & Pie, 2024. "Distinct mesenchymal cell states mediate prostate cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:461:y:2009:i:7263:d:10.1038_nature08361. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.