Shen M M, Wang X, Economides K D, Walker D, Abate-Shen C
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Cold Spring Harb Symp Quant Biol. 2008;73:529-38. doi: 10.1101/sqb.2008.73.050. Epub 2009 Jan 15.
The identification of stem cell/progenitor populations represents a critical step for deducing the putative cell type(s) of origin for epithelial cancers and may provide important therapeutic insights. In the case of the prostate gland, recent studies have made significant progress in the identification of candidate stem cell populations, but they have left unresolved key questions about their tissue localization and functional properties. In our work, we have used genetic lineage marking in vivo to demonstrate that a rare epithelial cell population marked by expression of the Nkx3.1 homeobox gene in the androgen-deprived prostate contains bipotential progenitor cells that are capable of self-renewal. Inducible targeting of the Pten tumor suppressor in these castrate-resistant Nkx3.1-expressing cells demonstrates that this stem/progenitor population is also a potent cell of origin for prostate cancer in mouse models. These findings may help to explain several intriguing features of prostate cancer and its phenotypic progression.
鉴定干细胞/祖细胞群体是推断上皮癌假定起源细胞类型的关键步骤，可能提供重要的治疗见解。就前列腺而言，最近的研究在鉴定候选干细胞群体方面取得了重大进展，但关于它们的组织定位和功能特性仍存在关键问题未解决。在我们的研究中，我们利用体内遗传谱系标记来证明，在雄激素剥夺的前列腺中，由Nkx3.1同源框基因表达标记的罕见上皮细胞群体包含能够自我更新的双能祖细胞。在这些去势抵抗性表达Nkx3.1的细胞中对Pten肿瘤抑制因子进行诱导性靶向，表明该干细胞/祖细胞群体也是小鼠模型中前列腺癌的有效起源细胞。这些发现可能有助于解释前列腺癌的几个有趣特征及其表型进展。
