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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
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    Cited by:

    1. 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.

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