Pre-malignant nasopharyngeal epithelial cell models.
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.
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China.
Qing-Li
QL
Kong
Su
S
Guan
Bao-Hong
BH
Guo
Mu-Sheng
MS
Zeng
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002877:Chromosomes, Human / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections; D004854:Herpesvirus 4, Human; D006801:Humans; D008954:Models, Biological; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000821:virology; D009305:Nasopharynx / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; C069077:BMI1 protein, human; C068651:E6 protein, Human papillomavirus type 16; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D063150:Polycomb Repressive Complex 1; C509186:TERT protein, human; D019098:Telomerase