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

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 and Michael M. Shen ()
Additional contact information
Xi Wang: Department of Medicine,
Marianna Kruithof- de Julio: Department of Medicine,
Kyriakos D. Economides: Center for Advanced Biotechnology and Medicine,
David Walker: Center for Advanced Biotechnology and Medicine,
Hailong Yu: Center for Advanced Biotechnology and Medicine,
M. Vivienne Halili: Center for Advanced Biotechnology and Medicine,
Ya-Ping Hu: Center for Advanced Biotechnology and Medicine,
Sandy M. Price: Center for Advanced Biotechnology and Medicine,
Cory Abate-Shen: and
Michael M. Shen: Department of Medicine,

Nature, 2009, vol. 461, issue 7263, 495-500

Abstract: 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.

Date: 2009
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DOI: 10.1038/nature08361

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