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Biological Consequences of Overexpression of a Transfected c-erbB-2 Gene in Immortalized Human Bronchial Epithelial Cells¹

Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892 [M. N., M. M., W. B., F. H., C. C. H., B. I. G.], and Lombardi Cancer Center, Georgetown University, School of Medicine, Washington, DC 20007 [R. L.]

In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithellal cells, a human c-erbB-2 expression vector was introduced into the simian virus 40 large T-antigen-immortalized human bronchial epithelial cell line BEAS-2B. Isolation of multiple clonal cell lines after selection revealed a wide range of expression of the gene product gp185^erbB-2. While three of six clones tested expressed gp185^erbB-2 at levels detectable by immunocytochemistry, only one, B2BE6, induced adenocarcinoma-like tumors in athymic nude mice. Both a nontumorigenic clone, B2BE2, and a tumorigenic clone, B2BE6, expressed comparable amounts of gp185^erbB-2, which became phosphorylated on tyrosine in response to treatment with the c-erbB-2 ligands gp30 and p75. These data suggest that overexpression of c-erbB-2 in human bronchial epithelial cells can contribute to, but is not sufficient for, induction of tumorigenicity in this human model system.

¹ Supported in part by a Grant-in-Aid for Cancer Research and a Comprehensive 10-Year Strategy for Cancer Research from the Ministry of Health and Welfare, Japan (M. N.).

² Present address: Pathology Division, National Cancer Center Research Institute, 1-1, Tsukuji 5-chome, Chuo-ku, Tokyo 104, Japan.

³ Present address: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98, Kasugade-naka, Konohana-ku, Osaka 554, Japan.

⁴ To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Building 37, Room 2C08, Bethesda, MD 20892.

Received 11/18/92. Accepted 2/24/93.

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