Abstract
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. ΔEGFR). 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.ΔEGFR cells than in the other two cell lines. The increased inhibitory response of U87MG.ΔEGFR cells was due to a greater sensitivity of the constitutively autophosphorylated Mr 140,000 and 155,000 ΔEGFR species to AG 1478. These results suggest that AG 1478 is a relatively specific inhibitor of the ΔEGFR, and this finding may have important therapeutic implications since the ΔEGFR occurs frequently in glioblastomas and in breast, lung, and ovarian cancers.
Footnotes
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↵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 June 6, 1996.
- Accepted July 16, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 17
