Carcinogenesis Advance Access originally published online on January 27, 2005
Carcinogenesis 2005 26(4):725-731; doi:10.1093/carcin/bgi016
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Carcinogenesis vol.26 no.4 © Oxford University Press 2005; all rights reserved.
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Immortalization of human small airway epithelial cells by ectopic expression of telomerase
1 Center for Radiological Research, College of Physicians and Surgeons and 2 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA and 3 International Space Radiation Laboratory, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
* To whom correspondence should be addressed at: Center for Radiological Research, Columbia University, 630 West 168th Street, New York, NY 10032, USA. Tel: +1 212 305 0846; Fax: +1 212 305 3229; Email: cp16{at}columbia.edu
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.
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