S. Kirchhoff et H. Hauser, Cooperative activity between HER oncogenes and the tumor suppressor IRF-1 results in apoptosis, ONCOGENE, 18(25), 1999, pp. 3725-3736
The tumor suppressor transcription factor IRE-I inhibits cell growth. In th
is report we show that IRF-1 also induces apoptosis of highly transformed a
nd tumorigenic cell lines. This activity of IRF-1 is demonstrated with cell
lines expressing HER oncogenes and an activatable IRE-I fusion protein. Gr
owth of cell lines expressing inactive HER1 is inhibited on IRE-I activatio
n. In contrast, the same cells are killed by apoptosis when HER1 and IRE-I
are activated simultaneously. We identified promoters stimulated synergisti
cally by IRF-1 and by activated HER1. To determine the signals causing tran
scriptional synergism and/or apoptosis we tried to modulate these effects b
y various dominant negative acting proteins. Dominant negative STAT5 alpha:
abolished both induction of apoptosis and transcriptional synergy of IRF-1
and HER. Thus, these results provide new insights into the mechanism of on
cogene-dependent apoptosis induced by the activation of a tumor suppressor.