Biological consequences of overexpression of a transfected c-erbB-2 gene in immortalized human bronchial epithelial cells.
In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithelial 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 gp185erbB-2. While three of six clones tested expressed gp185erbB-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 gp185erbB-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.
Noguchi
M
M
Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.
Murakami
M
M
Bennett
W
W
Lupu
R
R
Hui
F
F
Harris
C C
CC
Gerwin
B I
BI
D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004815:Epidermal Growth Factor; D019394:Ki-67 Antigen; D008024:Ligands; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; D014443:Tyrosine