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- Title
A luminal epithelial stem cell that is a cell of origin for prostate cancer.
- Authors
Xi Wang; Julio, Marianna Kruithof-de; Economides, Kyriakos D.; Walker, David; Hailong Yu; Halili, M. Vivienne; Ya-Ping Hu; Price, Sandy M.; Abate-Shen, Cory; Shen, Michael M.
- 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.
- Subjects
STEM cells; PROSTATE cancer; ONCOGENIC viruses; CELL transplantation; CELL proliferation; ANDROGENS; HOMEOBOX genes; CELLULAR therapy; BIOLOGICAL research
- Publication
Nature, 2009, Vol 461, Issue 7263, p495
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature08361