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

被引：554

作者：

Wang, Xi ^{[1
,2
,5
,6
]}

Kruithof-de Julio, Marianna ^{[1
,2
]}

Economides, Kyriakos D. ^{[5
,7
]}

Walker, David ^{[5
,6
]}

Yu, Hailong ^{[5
,6
]}

Halili, M. Vivienne ^{[5
,6
]}

Hu, Ya-Ping ^{[5
,6
]}

Price, Sandy M. ^{[5
,6
]}

Abate-Shen, Cory ^{[3
,4
,5
,7
]}

Shen, Michael M. ^{[1
,2
,5
,6
]}

机构：

[1] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA

[2] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA

[3] Columbia Univ Coll Phys & Surg, Dept Urol, New York, NY 10032 USA

[4] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[5] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

[6] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Piscataway, NJ 08854 USA

[7] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Piscataway, NJ 08854 USA

来源：

NATURE | 2009年 / 461卷 / 7263期

关键词：

ANDROGEN-INDUCED REGENERATION; BASAL-CELLS; RECOMBINASE ACTIVITY; TUMOR INITIATION; MOUSE PROSTATE; HOMEOBOX GENE; MUTANT MICE; IN-VIVO; NKX3.1; EXPRESSION;

D O I：

10.1038/nature08361

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：495 / U61

页数：8

共 51 条

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