Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1

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

“…In our study the combined activity of HER1 and IRF-1 in NIH3T3 cells leads to signi®cant cell death by apoptosis. This is in accordance with results obtained earlier with embryonic ®broblasts from IRF-1 7/7 in which expression of cHa-ras oncogene in wild type cells but not in IRF-1 7/7 cells forces the cells to undergo apoptosis under growth restricted conditions (Tanaka et al, 1994a). The combined activity of IRF-1 and HER1 is an example of oncogene dependent tumor suppressor mediated apoptosis.…”

“…Embryonic ®broblasts de®cient in IRF-1 genes become transformed by a single oncogene (c-Ha-ras). These cells do not undergo apoptosis upon c-Ha-ras oncogene expression and serum starvation whereas wild type cells harboring IRF-1 genes undergo programmed cell death (Tanaka et al, 1994a).…”

MyD genes in negative growth control

“…The transformed phenotype of ras-expressing IRF-17/7 MEFs could be suppressed by ectopic expression of IRF-1 cDNA. Moreover, it was observed that expression of the cHa-ras oncogene, when combined with a block to cell proliferation or treated by anti cancer drugs or ionizing radiation, resulted in apoptosis of the wildtype, but not the IRF-17/7, MEFs (Tanaka et al, 1994). Taken together these observations indicate that IRF-1 is a critical determinant of oncogeneinduced apoptosis IRF-1 was found to be involved in other apoptotic pathways as well.…”

Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells

“…The role of IRF-1 as a tumor suppressor is well established; for example, IRF-1À/À embryonic fibroblasts (EFs) are transformed by introduction of just one oncogene (Tanaka et al, 1994a), while wild type EFs usually require two. Also, NIH3T3 cells transformed by oncogenes c-myc and fosB can revert to a normal phenotype by ectopic expression of IRF-1 (Tanaka et al, 1994b).…”

“…Although IRF-1 has been shown to inhibit growth in response to agents such as IFN-g (Yim et al, 2003) and to mediate apoptosis in studies of IRF-1À/À cells, which are resistant to apoptosis (Tanaka et al, 1994a), it has been difficult to study the direct effects of IRF-1 expression since this growth inhibitory transcription factor makes it difficult to identify and expand stable transfectants (Kirchhoff et al, 1993). However, there have been several studies using inducible IRF-1 systems that have demonstrated apoptosis (Kirchhoff and Hauser, 1999;Sanceau et al, 2000).…”