A luminal epithelial stem cell that is a cell of origin for prostate cancer.
A luminal epithelial stem cell that is a cell of origin for prostate cancer.
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作者：
在上皮组织中，正常祖细胞和肿瘤起源细胞类型(S)之间的谱系关系一直知之甚少。在这里，我们展示了一种已知的前列腺上皮分化调节因子，同源盒基因Nkx3.1，标志着在前列腺再生过程中发挥作用的干细胞群体。遗传谱系标记表明，在没有睾丸雄激素的情况下表达Nkx3.1的稀有腔细胞(抗去势Nkx3.1表达细胞，CANS)是双潜能的，并且可以在体内自我更新，而单细胞移植实验表明CANS可以在移植肾中重建前列腺癌导管。Nkx3.1突变小鼠在一系列前列腺再生试验中的功能分析表明，Nkx3.1是干细胞维持所必需的。最后，靶向缺失CANS中的Pten肿瘤抑制基因会导致雄激素介导的再生后迅速形成肿瘤。这些观察表明，Carns代表了一种新的腔干细胞群体，是前列腺癌致癌转化的有效靶点。
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 which express Nkx3.1 in the absence of testicular androgens (castration-resistant Nkx3.1-expressing cells, CARNs) are bipotential and can self-renew in vivo, while 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 assays suggest that Nkx3.1 is required for stem cell maintenance. Finally, targeted deletion of the Pten tumor suppressor gene in CARNs results in rapid formation of carcinoma following androgen-mediated regeneration. These observations indicate that CARNs represent a novel luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.
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影响因子：
14.9
作者：
Indra, AK;Warot, X;Metzger, D
通讯作者：
Metzger, D
DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
2.5
作者：
Chen, H;Mutton, LN;Bieberich, CJ
通讯作者：
Bieberich, CJ
影响因子：
4.8
作者：
Bieberich, CJ;Fujita, K;Jay, G
通讯作者：
Jay, G
影响因子：
64.5
作者：
Kim, CFB;Jackson, EL;Jacks, T
通讯作者：
Jacks, T