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Malignant potential of H22 hepatocarcinoma cells increases after recovery from IFN‐γ‐mediated inhibition
Author(s) -
Gong Wei,
Ma KeZhong,
Liang Xinjun,
Liu YanYan,
Zhou Qing,
Zhang JiuLiang,
Chen HuaiYun,
Liu WenWei
Publication year - 2011
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20100268
Subject(s) - cyclin d1 , cancer research , apoptosis , mapk/erk pathway , irf1 , biology , interferon , kinase , signal transduction , interferon regulatory factors , cell growth , microbiology and biotechnology , transcription factor , gene , immunology , cell cycle , genetics
IFN‐γ (interferon γ) can effectively suppress tumours, but it has also been found to promote tumour progression. However, the underlying mechanisms by which it enhances malignancy have not been fully elucidated. By using a mouse model that expresses IFN‐γ locally in muscle, we found that the growth potential of tumours was increased after a quick decrease of IFN‐γ. Furthermore, the up‐regulation of IRF‐2 (IFN regulatory factor 2) and down‐regulation of IRF‐1 were also found in the tumour cells. Along these lines, IFN‐γ led to down‐regulated expression of cyclin‐D1, Bcl‐2 and Bcl‐xL and up‐regulated expression of p21 WAF1 and Bax in tumour cells. Yet, the expression of these genes, as well as activation of ERK (extracellular signal‐regulated kinase) and NF‐κB (nuclear factor‐κB), was also reversed shortly after a decrease in IFN‐γ, all of which resulted in increase tumour cell proliferation and apoptosis resistance. These findings indicate that the malignant potential of tumour cells may be suppressed by interfering with IRF‐2 signalling pathways during and after decreased IFN‐γ in tumour microenvironments.