INHIBITION OF HUMAN LUNG-CANCER CELL-LINE GROWTH BY AN ANTI-P185(HER2) ANTIBODY

p185HER2, the product of the c-erbB-2 or HER2 gene, is a membrane-boun d tyrosine kinase that has structural similarity to the epidermal grow th factor receptor. Functionally, interaction of HER2 with its ligand or p185HER2 antibodies affects the growth and differentiation of HER2- expressing breast cancer cell lines. As p185HER2 is also expressed in human lung cancers and human lung cancer cell lines, we hypothesized t hat these cell lines would also respond to p185HER2 antibodies. To tes t this hypothesis, we cultured human non-small cell lung cancer cell l ines in the presence of a p185HER2 monoclonal antibody called 4D5. 4D5 inhibited the growth of p185HER2-expressing cell lines in a dose-depe ndent fashion. In addition, BEAS.2B, a p185HER2-nonexpressing bronchia l epithelial cell line, was transfected with the HER2 cDNA, resulting in high-level p185HER2 expression, and growth of BEAS.HER2 was now inh ibited by 4D5 exposure. Mechanistically, 4D5 appeared to have a weak a gonist effect on the tyrosine kinase function of p185HER2, as exposure of p185HER2-expressing cell lines to 4D5 resulted in increased p185HE R2 phosphorylation. Furthermore, inhibition of tyrosine kinase functio n with Genistein reversed the 4D5-induced growth inhibition. Therefore , 4D5 can regulate the growth of p185HER2-expressing lung cancer cell lines through agonist effects on p185HER2.