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Brain Tumor and Stroke Research Laboratory, Department of Neurosurgery, Biomedical Research Institute, Louisiana State University Medical Center, Shreveport, Louisiana 71130 [Y. H., C. G. C., A. N.], and Ludwig Institute for Cancer Research, Department of Medicine [W. K. C., H-J. S. H.], and Center for Molecular Genetics [W. K. C.], University of California at San Diego, La Jolla, California 92093-0660
The effects of a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, tyrphostin AG 1478, were tested on three related human glioma cell lines: U87MG, which expressed endogenous wild-type (wt) EGFR, and two retrovirally infected U87MG cell populations which overexpressed either wt (U87MG.wtEGFR) or truncated EGFR (U87MG. 
EGFR). Although AG 1478 inhibited cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor autophosphorylation of each cell line in a dose-dependent manner, it was significantly more potent in U87MG.EGFR cells than in the other two cell lines. The increased inhibitory response of U87MG.EGFR cells was due to a greater sensitivity of the constitutively autophosphorylated Mr 140,000 and 155,000 EGFR species to AG 1478. These results suggest that AG 1478 is a relatively specific inhibitor of the EGFR, and this finding may have important therapeutic implications since the EGFR occurs frequently in glioblastomas and in breast, lung, and ovarian cancers.
1 To whom requests for reprints should be addressed, at Department of Neurosurgery, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130.
Received 6/ 6/96. Accepted 7/16/96.
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