Gray G E, Mann R S, Mitsiadis E, Henrique D, Carcangiu M L, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Am J Pathol. 1999 Mar;154(3):785-94. doi: 10.1016/S0002-9440(10)65325-4.
During development, the Notch signaling pathway is essential for the appropriate differentiation of many cell types in organisms across the phylogenetic scale, including humans. Notch signaling is also implicated in human diseases, including a leukemia and two hereditary syndromes known as Alagille and CADASIL. To generate tools for pursuing the role of the Notch pathway in human disease and development, we have cloned and analyzed the expression of three human homologues of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2), and human Delta1 (H-Delta-1), and determined their chromosomal localizations. We have also raised antibodies to HJ1, and used these antibodies in conjunction with in situ hybridization to examine the expression of these ligands in normal and cancerous cervical tissue. We find that, as reported previously for Notch, the ligands are up-regulated in certain neoplastic tissues. This observation is consistent with the notion that Notch signaling is an important element in these pathogenic conditions, raising the possibility that modulation of Notch activity could be used to influence the fate of the cells and offering a conceivable therapeutic avenue.
在发育过程中，Notch信号通路对于包括人类在内的整个系统发育范围内生物体中多种细胞类型的适当分化至关重要。Notch信号也与人类疾病有关，包括一种白血病以及两种称为阿拉吉列综合征（Alagille）和大脑常染色体显性动脉病伴皮质下梗死和白质脑病（CADASIL）的遗传性综合征。为了生成用于探究Notch信号通路在人类疾病和发育中作用的工具，我们克隆并分析了Notch配体Delta和Serrate的三个人类同源物，即人类锯齿蛋白1（HJ1）、人类锯齿蛋白2（HJ2）和人类Delta1（H-Delta-1）的表达，并确定了它们的染色体定位。我们还制备了针对HJ1的抗体，并将这些抗体与原位杂交结合使用，以检查这些配体在正常和癌性宫颈组织中的表达。我们发现，正如先前关于Notch的报道一样，这些配体在某些肿瘤组织中上调。这一观察结果与Notch信号是这些致病条件中的重要因素这一观点一致，这增加了调节Notch活性可用于影响细胞命运的可能性，并提供了一种可行的治疗途径。
