癌前鼻咽上皮细胞模型(英文)

Pre-malignant nasopharyngeal epithelial cell models

研究鼻咽癌进展的实验模型系统可以为鼻咽癌发生的分子机制研究及潜在的临床干预措施提供有价值的信息。由于EB病毒仅感染人类及少数灵长类,目前尚缺乏有代表性的鼻咽癌动物模型。当前鼻咽癌早期发生的体外模型的建立主要采用使正常增殖的鼻咽上皮细胞转化为永生化细胞的方法。最早的两株永生化鼻咽上皮细胞是由外源表达SV40T及HPVE6/E7病毒癌基因诱导建立,并进行了验证。为了避免由病毒癌基因引起的一系列与鼻咽癌发生不相关的分子改变,我们利用在鼻咽癌细胞和组织中高表达的癌基因Bmi-1,介导建立并验证了两株永生化鼻咽上皮细胞。另外,由人端粒酶逆转录酶诱导产生的永生化鼻咽上皮细胞也已建立。与由病毒癌基因诱导产生的永生化细胞不同,这些永生化的鼻咽上皮细胞保留了正常的P53表达水平,除一些在鼻咽癌中存在的分子改变外,并未表现出其他的基因缺陷。因此,这些永生化的细胞可以用于由某些特定的分子遗传因素诱导的鼻咽癌进展的研究,特别是可以用于阐明EB病毒在鼻咽癌发展中所起的作用。

Experimental models that allow investigation of nasopharyngeal carcinoma（NPC） progression could provide valuable insights of the molecular mechanism of nasopharyngeal carcinogenesis as well as potential clinical intervention. Because Epstein-Barr virus only infects humans and a few species of monkeys, representative NPC animal models have not been available so far. Attempts to provide cell models for early nasopharyngeal carcinogenesis have involved in the studies of in vitro transformation of normal finite lifespan human nasopharyngeal epithelial cells （NPEC） to immortality. The first two immortalized NPECs were established by introduction of ectopic SV40T or HPV E6/E7. In order to avoid the unrelated molecular alterations caused by the viral oncogenes, we established and characterized two immortalized NPECs by introduction of Bmi-1, an oncogene which has been demonstrated to be overexpressed in NPC cells and specimens. In addition, human telomerase reverse transcriptase （hTERT） immortalized NPECs have been established in both Tsao＇s and our laboratory. Unlike the immortalized cells induced by viral oncogenes, these immortal NPECs maintain a normal p53 checkpoint, and are unlikely to have other undefined genetic lesions except presenting some molecular alterations which have been observed in NPC. Thus, the establishment of the immortalized NPECs can be used to further study the mechanism of NPC development using defined genetic elements, particularly in elucidating the role of EBV infection in NPC development.