Malignant potential of H22 hepatocarcinoma cells increases after recovery from IFN-γ-mediated inhibition.
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 p21WAF1 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.
Department of Oncology, Xiangfan Hospital Xiangfan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Xiangfan, Peoples Republic of China.
Wei
W
Gong
Ke-Zhong
KZ
Ma
Xinjun
X
Liang
YanYan
Y
Liu
Qing
Q
Zhou
JiuLiang
J
Zhang
HuaiYun
H
Chen
Wen-Wei
WW
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D007273:Injections, Intramuscular; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation
D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D007371:Interferon-gamma