Leong Kevin G, Gao Wei-Qiang
Department of Molecular Biology, Genentech Inc., 1 DNA Way Southern San Francisco, CA 94080, USA.
Differentiation. 2008 Jul;76(6):699-716. doi: 10.1111/j.1432-0436.2008.00288.x. Epub 2008 Jun 28.
The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.
跨膜受体Notch家族是细胞命运决定的重要调节因子。因此，Notch信号通路与众多组织的发育密切相关。最近的研究结果突出了Notch信号通路在正常前列腺发育中的关键作用。胚胎期和出生后前列腺的生长与发育、前列腺内细胞谱系的正常分化以及去势和激素替代后成年前列腺的维持与再生均需要Notch信号通路。Notch作为前列腺癌发生、发展和转移调节因子的证据也已出现。本综述总结了我们目前对Notch信号通路元件在前列腺发育和肿瘤发生中作用的理解，这些元件包括锯齿状蛋白家族、Delta样蛋白家族、毛状/分裂增强子家族以及与YRPW基序相关的毛状/分裂增强子家族成员。文中还展示了支持Notch信号通路元件在前列腺肿瘤中作为癌基因和肿瘤抑制因子的数据，以及表明Notch受体和配体作为正常前列腺干/祖细胞和前列腺癌干/起始细胞潜在标志物的数据。
