Immortalization of human small airway epithelial cells by ectopic expression of telomerase.
Two immortalized human airway epithelial cell lines were established by the ectopic expression of human telomerase reverse transcriptase (hTERT). These cell lines have been continuously cultured for >200 population doublings (PDs). They are characterized by an overexpression of hTERT mRNA, elongated telomere length and higher telomerase activity. Early passage of these cells (<20 PDs) expressed the p16 protein at a level comparable to their parental cells. In later passages (>150 PDs), p16 protein was decreased but recovered to the early passage level upon treatment with a methylation inhibitor, 5-Aza-CdR. Chromosome analysis showed a near-diploid karyotype albeit with a gain or loss of certain chromosomes and a few stable translocations in both cell lines. No p53 gene alterations were found in these cell lines. They remained anchorage dependent in growth and were non-tumorigenic in nude mice. These two cell lines are the first reported immortalized human airway epithelial cell lines by hTERT expression without incorporation of virus or other genes, which may serve as a useful model system for studies on bronchial carcinogenesis.
Piao
Chang Q
CQ
Center for Radiological Research, College of Physicians and Surgens, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. cp16@columbia.edu
Liu
Li
L
Zhao
Yong L
YL
Balajee
Adayabalam S
AS
Suzuki
Masao
M
Hei
Tom K
TK
D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D004171:Diploidy; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D007621:Karyotyping; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase