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Carcinogenesis Advance Access published online on January 27, 2005

Carcinogenesis, doi:10.1093/carcin/bgi016
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Oxford University Press
Received July 20, 2004
Revised December 23, 2004
Accepted January 8, 2005

CANCER BIOLOGY

Immortalization of human small airway epithelial cells by ectopic expression of telomerase

Chang Q. Piao 1*, Li Liu 1, Yong L. Zhao 1, Adayabalam S. Balajee 1, Masao Suzuki 2, and Tom K. Hei 3

1 Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, NY 10032
2 International Space Radiation Laboratory, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
3 Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, NY 10032; Department of Environmental Health Sciences, Mailman School of Public health, Columbia University, New York, NY 10032

* To whom correspondence should be addressed.
Chang Q. Piao, E-mail: cp16{at}columbia.edu


   Abstract

Two immortalized human airway epithelial cell lines were established by ectopic expression of hTERT. These cell lines have been continuously cultured for over 200 population doublings. They are characterized by over-expression of hTERT mRNA, elongated telomere length and higher telomerase activity. Early passage of these cells (<20 population doublings) expressed the p16 protein at a level comparable to their parental cells. In later passages (>150 population doublings), 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 virus or other genes incorporation, which may serve as a useful model system for studies on bronchial carcinogenesis.


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