Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
J Oral Pathol Med. 2010 Aug 1;39(7):552-8. doi: 10.1111/j.1600-0714.2009.00871.x. Epub 2010 Mar 9.
In mammals, the Notch gene family encodes four receptors (Notch1-4), and all of them are important for cell fate decisions. Notch signaling pathway plays an essential role in tooth development. The ameloblastoma, a benign odontogenic epithelial neoplasm, histologically recapitulates the enamel organ at bell stage. Notch has been detected in the plexiform and follicular ameloblastoma. Its activity in the desmoplastic ameloblastoma is unknown.
Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) were examined immunohistochemically in 10 cases of desmoplastic ameloblastoma.
Ameloblastoma tumor epithelium demonstrated positive expression for Notch1 (n = 5/10), Notch3 (n = 8/10), Notch4 (n = 10/10), Jagged1 (n = 6/10) and Delta1 (n = 5/10), but no reactivity for Notch2 (n = 10/10) and Jagged2 (10/10). Expression patterns were distinct with some overlap. Positive activity was detected largely in the cell membrane and cytoplasm of peripheral and central neoplastic epithelial cells, and sometimes in the nucleus. Staining score was highest for Notch4. Stromal components namely endothelial cells and fibroblasts showed overexpression for Notch4 but were mildly or non-reactive for the other Notch members and their ligands.
These findings suggest that Notch receptors and their ligands may play differing roles during the development of the desmoplastic ameloblastoma with Notch4 probably playing a greater role in the acquisition of tissue-specific cellular characteristics in the desmoplastic ameloblastoma.
在哺乳动物中,Notch 基因家族编码四个受体(Notch1-4),它们在细胞命运决定中都很重要。Notch 信号通路在牙齿发育中起着至关重要的作用。成釉细胞瘤是一种良性牙源性上皮性肿瘤,组织学上重现钟状期的釉器。已经在丛状型和滤泡型成釉细胞瘤中检测到 Notch。其在促结缔组织增生型成釉细胞瘤中的活性尚不清楚。
采用免疫组织化学方法检测 10 例促结缔组织增生型成釉细胞瘤中 Notch1-4 及其配体(Jagged1、Jagged2 和 Delta1)的表达。
成釉细胞瘤肿瘤上皮表达 Notch1(n = 5/10)、Notch3(n = 8/10)、Notch4(n = 10/10)、Jagged1(n = 6/10)和 Delta1(n = 5/10),但不表达 Notch2(n = 10/10)和 Jagged2(n = 10/10)。表达模式存在一定的重叠。阳性活性主要在肿瘤上皮细胞的细胞膜和细胞质中检测到,有时也在细胞核中检测到。Notch4 的染色评分最高。间质成分,即内皮细胞和成纤维细胞,过度表达 Notch4,但对其他 Notch 成员及其配体呈轻度或无反应。
这些发现表明,Notch 受体及其配体可能在促结缔组织增生型成釉细胞瘤的发展中发挥不同的作用,Notch4 可能在促结缔组织增生型成釉细胞瘤中获得组织特异性细胞特征方面发挥更大的作用。