Open Access

Stéphan Jalaguier, Axel Kuehn, Chloé Petitpas, Arnaud Dulom, Rémy Jacquemont, Cindy Assi, Sophie Sixou, Udo Jeschke, Jacques Colinge, Vincent Cavaillès

• RIP140 (receptor interacting protein of 140 kDa) is an important player in breast cancer (BC) by regulating key cellular pathways such as nuclear hormone receptor signaling. In order to identify additional genes specifically regulated by RIP140 in BC, we performed a transcriptomic analysis after silencing its expression in MCF-7 cells. We identified the interferon γ (IFNγ) signaling as being substantially repressed by RIP140 knockdown. Using the GBP1 (guanylate binding protein 1) gene as a reporter of IFNγ signaling, we demonstrated its robust induction by RIP140 through an ISRE motif, leading to a significant reduction of its induction upon IFNγ treatment. Furthermore, we showed that low levels of RIP140 amplified the IFNγ-dependent inhibition of BC cell proliferation. In line with these data, reanalysis of transcriptomic data obtained in human BC samples revealed that IFNγ levels were associated with good prognosis only for BC patients exhibiting tumors expressing low levels ofRIP140 (receptor interacting protein of 140 kDa) is an important player in breast cancer (BC) by regulating key cellular pathways such as nuclear hormone receptor signaling. In order to identify additional genes specifically regulated by RIP140 in BC, we performed a transcriptomic analysis after silencing its expression in MCF-7 cells. We identified the interferon γ (IFNγ) signaling as being substantially repressed by RIP140 knockdown. Using the GBP1 (guanylate binding protein 1) gene as a reporter of IFNγ signaling, we demonstrated its robust induction by RIP140 through an ISRE motif, leading to a significant reduction of its induction upon IFNγ treatment. Furthermore, we showed that low levels of RIP140 amplified the IFNγ-dependent inhibition of BC cell proliferation. In line with these data, reanalysis of transcriptomic data obtained in human BC samples revealed that IFNγ levels were associated with good prognosis only for BC patients exhibiting tumors expressing low levels of RIP140, thus confirming its effect on the anti-tumor activity of IFNγ provided by our experimental data. Altogether, this study identifies RIP140 as a new regulator of IFNγ signaling in breast tumorigenesis.…