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Inhibition of tumor growth by ERK1/2 inhibitors is associated with the induction of interferon‐γ production (397.3)
Author(s) -
Ma Xingzhe,
Wang Qixue,
Duan Yajun,
Han Jihong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.397.3
Subject(s) - carcinogenesis , in vivo , cytokine , interferon , growth inhibition , cancer research , biology , cell growth , gene expression , chemistry , cancer , gene , immunology , biochemistry , genetics
Inhibition of tumor growth by ERK1/2 inhibitors is associated with the induction of interferon‐γ production Xingzhe Ma, Qixue Wang, Yajun Duan, Jihong Han State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China ERK1/2 plays an important role in cell survival, proliferation and differentiation. However, the high ERK1/2 activity has been linked to tumorigenesis. Several ERK1/2 inhibitors are in clinical trials to evaluate their effects on cancers. IFN‐γ is an important cytokine with anti‐tumorigenic function. So far, it has been remained unknown if the anti‐cancer action of ERK1/2 inhibitors is related to their effect on IFN‐γ expression. We previously reported that activation of LXR induces IFN‐γ expression and inhibits tumor growth, and ERK1/2 inhibitors can activate LXR‐targeted gene expression. Herein, we determined if ERK1/2 inhibitors can influence IFN‐γ expression, and the anti‐tumorigenic action of ERK1/2 inhibitors is completed, in part, by their effect on IFN‐γ production. We observed that ERK1/2 inhibitors increased IFN‐γ protein expression which was associated with increased IFN‐γ mRNA expression, promoter activity and formation of LXRE‐nuclear protein complexes. In vivo , U0126 increased mouse serum IFN‐γ levels and IFN‐γ expression in tissues. Animal study also demonstrated that U0126 inhibited inoculated LLC1 tumor growth in wild type but not in IFN‐γ ‐/‐ mice indicating the inhibition is associated with IFN‐γ production. Our study suggests that ERK1/2 inhibitor induces IFN‐γ production and the induction can be partially attributed to their anti‐tumorigenic properties.