Publication Date:
2009-09-11
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800362/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800362/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xi -- Kruithof-de Julio, Marianna -- Economides, Kyriakos D -- Walker, David -- Yu, Hailong -- Halili, M Vivienne -- Hu, Ya-Ping -- Price, Sandy M -- Abate-Shen, Cory -- Shen, Michael M -- P01 CA154293/CA/NCI NIH HHS/ -- R01 DK076602/DK/NIDDK NIH HHS/ -- R01 DK076602-05/DK/NIDDK NIH HHS/ -- U01 CA084294/CA/NCI NIH HHS/ -- U01 CA084294-10/CA/NCI NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):495-500. doi: 10.1038/nature08361. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741607" target="_blank"〉PubMed〈/a〉
Keywords:
Androgens/deficiency/metabolism
;
Animals
;
Castration
;
Cell Differentiation
;
Cell Division
;
*Cell Lineage
;
Cell Transformation, Neoplastic
;
Epithelial Cells/metabolism/*pathology/transplantation
;
Gene Expression Regulation
;
Homeodomain Proteins/genetics/metabolism
;
Kidney
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Nude
;
Neoplastic Stem Cells/metabolism/*pathology/transplantation
;
PTEN Phosphohydrolase/deficiency/genetics
;
Prostatic Neoplasms/genetics/metabolism/*pathology
;
Regeneration
;
Transcription Factors/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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