Cooperative activity between HER oncogenes and the tumor suppressor IRF-1 results in apoptosis.

Abstract:

:The tumor suppressor transcription factor IRF-1 inhibits cell growth. In this report we show that IRF-1 also induces apoptosis of highly transformed and tumorigenic cell lines. This activity of IRF-1 is demonstrated with cell lines expressing HER oncogenes and an activatable IRF-1 fusion protein. Growth of cell lines expressing inactive HER1 is inhibited on IRF-1 activation. In contrast, the same cells are killed by apoptosis when HER1 and IRF-1 are activated simultaneously. We identified promoters stimulated synergistically by IRF-1 and by activated HER1. To determine the signals causing transcriptional synergism and/or apoptosis we tried to modulate these effects by various dominant negative acting proteins. Dominant negative STAT5alpha abolished both induction of apoptosis and transcriptional synergy of IRF-1 and HER. Thus, these results provide new insights into the mechanism of oncogene-dependent apoptosis induced by the activation of a tumor suppressor.

journal_name

Oncogene

journal_title

Oncogene

authors

Kirchhoff S,Hauser H

doi

10.1038/sj.onc.1202704

subject

Has Abstract

pub_date

1999-06-24 00:00:00

pages

3725-36

issue

25

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

杂志文章

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