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Development of Tumorigenicity in Simian Virus 40-immortalized Human Bronchial Epithelial Cell Lines¹

Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia [R. R. R., S. E. S.]; Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892 [R. R. R., J. C. W., Y. K., B. I. G., J. F. L., C. C. H.]; and Huntington Medical Research Institutes, Pasadena, California 91101 [Y. O.]

Of five SV40-transformed clonal human bronchial epithelial cell lines previously shown to be nontumorigenic at early passages (R. R. Reddel et al., Cancer Res., 48: 1904–1909, 1988), two lines (BES-1A1 and BEAS-2B) from different donors have become weakly tumorigenic with further passaging. BES-1A1 passage 26 cells formed tumors in 3 of 9 athymic nude mice given s.c. injections, whereas BEAS-2B cells of 32 passages formed highly cystic tumors at 8 of 58 injection sites after long latency periods [17 ± 7 (SD) weeks]. These tumors took a total of 36 ± 8 weeks to reach a diameter of 1.0 cm. Tumor cell lines were established from four BE-AS-2B tumors, and these are resistant to the growth-inhibitory effects of serum, an inducer of squamous differentiation in BEAS-2B and normal bronchial epithelial cells. This finding supports the hypothesis that development of resistance to inducers of terminal squamous differentiation may be a step in the process of bronchial carcinogenesis. One of these tumor cell lines, B39-TL, is significantly more tumorigenic than the others and has a deletion from the short arm of chromosome 3 as has been described previously for some naturally occurring human bronchial carcinomas. Thus, from the clonally derived BEAS-2B cell line, cell populations with various degrees of tumorigenicity have developed. Analysis of the changes in these cells may yield insights into the multiple events involved in acquisition of the tumorigenic phenotype.

¹ This study was supported in part by a project grant from the University of Sydney Cancer Research Fund.

² To whom requests for reprints should be addressed, at Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia.

³ Present address: University of Rochester, Rochester, NY 14642.

⁴ Present address: Beijing Institute for Cancer Research, Western District, Beijing, People's Republic of China.

⁵ Present address: Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Inc., Albuquerque, NM 87185.

Received 6/ 8/92. Accepted 12/22/92.

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