| First Author | Wang X | Year | 2009 |
| Journal | Nature | Volume | 461 |
| Issue | 7263 | Pages | 495-500 |
| PubMed ID | 19741607 | Mgi Jnum | J:153425 |
| Mgi Id | MGI:4365464 | Doi | 10.1038/nature08361 |
| Citation | Wang X, et al. (2009) A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461(7263):495-500 |
| abstractText | 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. |
