Critical role for constitutive type I interferon signaling in the prevention of cellular transformation

被引：47

作者：

Chen, Hui-min ^{[1
,2
,3
]}

Tanaka, Nobuyuki ^{[1
,2
]}

Mitani, Yukiko ^{[1
,2
]}

Oda, Eri ^{[1
,2
]}

Nozawa, Hiroaki ^{[1
,2
]}

Chen, Jian-zhong ^{[1
,2
]}

Yanai, Hideyuki ^{[1
,2
]}

Negishi, Hideo ^{[1
,2
]}

Choi, Myoung Kwon ^{[1
,2
]}

Iwasaki, Toshiroh

Yamamoto, Hiroyuki ^{[4
]}

Taniguchi, Tadatsugu ^{[1
,2
]}

Takaoka, Akinori ^{[1
,2
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1130033, Japan

[2] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan

[3] Tokyo Univ Agr & Technol, Dept Vet Internal Med, Fuchu, Tokyo 1838509, Japan

[4] Sapporo Med Univ, Dept Internal Med 1, Chuo Ku, Sapporo, Hokkaido 0608543, Japan

来源：

CANCER SCIENCE | 2009年 / 100卷 / 03期

关键词：

TRANSCRIPTION FACTOR IRF-1; MESSENGER-RNA; CROSS-TALK; ALPHA; P53; GENE; ACTIVATION; APOPTOSIS; RESPONSES; PATHWAYS;

D O I：

10.1111/j.1349-7006.2008.01051.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Interferons-alpha/beta, which are produced upon viral infection, are key soluble factors for the establishment of an antiviral state, but are also produced at low levels in the absence of infection. Herein, we demonstrate that a weak signal by these constitutively produced IFN-alpha/beta show a preventive role in cellular transformation. Ifnar1-deficient (Ifnar1(-/-)) MEF, which are devoid of IFN-alpha/beta signal, undergo a spontaneous transformation during long-term cell culture. Similar to Irf1(-/-) MEF, primary Ifnar1(-/-) MEF become tumorigenic in nude mice by the expression of activated c-Ha-Ras oncoprotein. However, Ifnar1(-/-) MEF do not show any abnormal growth properties. A similar observation is made in Ifnb(-/-) MEF that fail to produce constitutive IFN-alpha/beta, whereas such a transforming property is not found in MEF that lack any of the IFN receptor downstream molecules including Stat1, IRF9 and IRF1. Furthermore, Ifnar1(-/-) mice develop chemically-induced skin papilloma more severely than wild-type mice. In addition, the expression levels of IFNAR1 mRNA are significantly decreased in human gastric cancer tissues. These results suggest a cell-intrinsic role of the weak signal by constitutively produced IFN-alpha/beta to prevent cells from transformation, which may be mediated by a hitherto-unknown pathway(s) downstream of the IFN-alpha/beta receptor. (Cancer Sci 2009; 100: 449-456).

引用

页码：449 / 456

页数：8

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