RRC ID 53982
著者 Yamaguchi H, Hiroi M, Ohmori Y.
タイトル Silencing of the interferon-inducible gene Ifi204/p204 induces resistance to interferon-γ-mediated cell growth arrest of tumor cells.
ジャーナル Cytokine
Abstract Many tumor cells escape from cancer immunosurveillance and resist treatment with interferons (IFNs). Although the mechanism underlying IFN resistance is mostly attributed to a deficiency of components of the IFN-signaling pathway, some types of tumor cells resist IFN-mediated cell growth arrest despite the presence of an intact JAK/STAT signaling pathway. However, the molecular mechanisms underlying the unresponsiveness to IFNs independent of the defective JAK/STAT pathway remain to be clarified. To elucidate the mechanisms underlying IFNγ resistance, we examined the anti-proliferative effect of IFNγ on mouse tumor cell lines. Mouse squamous cell carcinoma (SCCVII) cells were resistant to IFNγ-mediated cell growth arrest despite the presence of the IFNγ-induced STAT1-dependent signaling pathway, whereas IFNγ inhibited cell growth of B16/F1 cells, a well-known IFNγ-sensitive mouse melanoma cell line, at the G1 phase of the cell cycle. Treatment of SCCVII cells with IFNγ neither downregulated the expression of cyclin D1, cyclin A2, and cyclin E1 nor induced a hypo-phosphorylated, active form of retinoblastoma protein (pRb). Interestingly, the hyper-phosphorylated, inactive form of pRb was exclusively localized in the cytoplasm in SCCVII cells. The IFN-inducible 204 gene (Ifi204), whose gene product, p204, binds to pRb and exerts an anti-proliferative effect, was repressed in SCCVII cells. p204 overexpression in SCCVII significantly inhibited cell growth, and mutation of a pRb-binding LXCXE motif decreased the anti-proliferative effect. These results suggest that silencing of Ifi204/p204 induces resistance to IFNγ-mediated cell growth arrest in SCCVII cells.
巻・号 118
ページ 80-92
公開日 2019-6-1
DOI 10.1016/j.cyto.2018.06.029
PII S1043-4666(18)30279-5
PMID 30017387
MeSH Animals Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology Cell Cycle Proteins / genetics Cell Line, Tumor Cell Proliferation / genetics* Down-Regulation / genetics G1 Phase / genetics Growth Inhibitors / genetics* Interferon-gamma / genetics* Melanoma / genetics Melanoma / pathology Mice Nuclear Proteins / genetics* Phosphoproteins / genetics* Phosphorylation / genetics Protein Binding / genetics Retinoblastoma Protein / genetics Signal Transduction / genetics
IF 2.952
引用数 1
リソース情報
ヒト・動物細胞 B16 F1(RCB2649)