Yc. Han et al., TYRPHOSTIN AG-1478 PREFERENTIALLY INHIBITS HUMAN GLIOMA-CELLS EXPRESSING TRUNCATED RATHER THAN WILD-TYPE EPIDERMAL GROWTH-FACTOR RECEPTORS, Cancer research, 56(17), 1996, pp. 3859-3861
The effects of a new epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitor, tyrphostin AG 1478, were tested on three related hum
an glioma cell lines: U87MG, which expressed endogenous wild-type (wt)
EGFR, and two retrovirally infected U87MG cell populations which over
expressed either wt (U87MG.wtEGFR) or truncated EGFR (U87MG. Delta EGF
R). Although AG 1478 inhibited cell growth, DNA synthesis, EGFR tyrosi
ne kinase activity, and receptor autophosphorylation of each cell line
in a dose-dependent manner, it was significantly more potent in U87MG
.Delta EGFR cells than in the other two cell lines, The increased inhi
bitory response of U87MG.Delta EGFR cells was due to a greater sensiti
vity of the constitutively autophosphorylated M(r) 140,000 and 155,000
Delta EGFR species to AG 1478. These results suggest that AG 1478 is
a relatively specific inhibitor of the Delta EGFR, and this finding ma
y have important therapeutic implications since the Delta EGFR occurs
frequently in glioblastomas and in breast, lung, and ovarian cancers.