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- W2024577060 abstract "Interferons (IFNs) suppress cell growth by inducing cellular genes. The anti-estrogen tamoxifen (Tam), binds to estrogen receptor and inhibits transcription of estrogen stimulated genes. In cells resistant to IFN-induced growth suppression, IFN/Tam combination causes cell death. We previously reported that the combination of IFN-beta and Tam was a more potent growth suppressor of human tumor xenografts than either agent alone. The IFN/Tam combination acts in a manner similar to the IFN/retinoic acid combination. Using a genetic technique, we have recently identified several genes associated with retinoid-IFN-induced mortality (GRIM). One such gene, GRIM-12, was identical to human thioredoxin reductase (TR). In the present study we have examined whether the IFN/Tam combination also requires GRIM-12 for inducing cell death. We report here that GRIM-12 is necessary for mediating the cell death effects of IFN/Tam, and its expression is induced by IFN/Tam at a post-transcriptional stage. Repression of GRIM-12 levels either by antisense expression or by dominant negative inhibitors caused resistance to IFN/Tam induced death and promoted cell growth. Overexpression of GRIM-12 increased IFN/Tam induced apoptosis. Thus, these studies have identified a critical role for GRIM-12 (TR) in apoptosis." @default.
- W2024577060 created "2016-06-24" @default.
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- W2024577060 date "2000-04-01" @default.
- W2024577060 modified "2023-09-27" @default.
- W2024577060 title "The interferon-β and tamoxifen combination induces apoptosis using thioredoxin reductase" @default.
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- W2024577060 doi "https://doi.org/10.1016/s0167-4889(00)00021-5" @default.
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